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Purpose:The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223RaCl2) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers.Patients and Methods:A 3+3 phase I, dose-escalation trial of 223RaCl2 (50, 75, and 100 kBq/kg) was designed in patients with recurrent/metastatic osteosarcoma aged ≥15 years. Objective measurements included changes in standardized uptake values of positron emission tomography (PET; 18FDG and/or NaF-18) and single-photon emission CT/CT (99mTc-MDP) as well as alkaline phosphatase and bone turnover markers at baseline, midstudy, and the end of the study.Results:Among 18 patients enrolled (including 15 males) aged 15–71 years, tumor locations included spine (n = 12, 67%), pelvis (n = 10, 56%), ribs (n = 9, 50%), extremity (n = 7, 39%), and skull (n = 2, 11%). Patients received 1–6 cycles of 223RaCl2; cumulative doses were 6.84-57.81 MBq. NaF PET revealed more sites of metastases than did FDG PET. One patient showed a metabolic response on FDG PET and NaF PET. Four patients had mixed responses, and one patient had a response in a brain metastasis. Bronchopulmonary hemorrhage from Grade 3 thrombocytopenia (N = 1) was a DLT. The median overall survival time was 25 weeks.Conclusions:The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for 223RaCl2 in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies.

Supplementary file: Previous therapies, Overall survival S1 : Prior therapies of patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Table S2: Adverse events in patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Figure 1: Overall survival of patients with osteosarcoma enrolled on the Radium 223 trial. Supplementary Figure 2: Correlation of % change in RECIST with relative change in LDH. Table 3: Table 1. Ra-223 dichloride Dose Escalation scheme (N=3/cohort)

Malnutrition is associated with treatment-related toxicities (TRT) in adults with solid tumors and in children with leukemia. Few studies have assessed whether malnutrition in pediatric patients treated for solid tumors impacts risk for TRT, relapse, and/or survival. To address this knowledge gap, this retrospective study evaluated the association between body mass index (BMI) at diagnosis, and imputed BMI during therapy, on the prevalence of TRT, specific toxicities, relapse, and survival in pediatric patients with solid tumors treated with cisplatin-containing regimens. Kaplan–Meier curves and regression models evaluated the association between patient-specific characteristics (including BMI) and TRT, relapse, and survival. The cohort included 221 patients, of whom 22% were malnourished at diagnosis (10% were underweight and 12% were obese). Most patients (60%) experienced at least one severe TRT, and 30% developed more than one severe TRT. Most patients with obesity at diagnosis remained obese during therapy (62%). In multivariable analysis, obesity at diagnosis was significantly associated with a more than threefold greater risk for developing severe TRT (p = 0.037), specifically for acute or chronic kidney injury (p = 0.014). Obesity at diagnosis and adolescent and young adult age (≥15 years at diagnosis) were associated with worse event-free survival (hazard ratio [HR] 2.32, p = 0.024 and HR 2.28, p = 0.010, respectively) and overall survival (HR 3.69, p = 0.006 and HR 2.6, p = 0.012, respectively). Obese and older patients therefore constitute populations at risk for poorer outcomes. Prospective studies are warranted to gain further insight into the mechanism and role of obesity and adolescence in developing TRT and/or treatment failure.

BACKGROUND: Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD), the de-facto standard-of-care in adult-onset Hodgkin lymphoma (HL), has not been directly compared to doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), a pediatric-aimed regimen designed to reduce late-effects. We aimed to describe the single institution experience of using both regimens in patients with pediatric HL. METHODS: This retrospective cohort study evaluated a total of 224 patients diagnosed with HL between 1999 and 2018 at Children’s Hospital Los Angeles (CHLA), of which 93 patients were eligible having received ABVD (n=46) or ABVE-PC (n=47) chemotherapy as their initial treatment. Descriptive analyses were performed using the Student’s t-test or Fisher’s exact test. Survival analysis used the Kaplan-Meier method. Events included death, relapse and secondary malignancy. We also describe the use of radiation therapy, pulmonary toxicity and cardiomyopathy determined by shortening fraction

Background Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as

The purpose of this study is to evaluate the clinical, pathologic, and multimodality cross-sectional imaging features of a cohort of 94 patients with desmoplastic small round cell tumor (DSRCT).This retrospective study of 94 patients with pathologically verified DSRCT was conducted at a tertiary cancer center between 2001 and 2013. Epidemiologic, clinical, pathologic, and imaging findings were recorded. Tumor size, location, and shape and the distribution pattern of metastases at presentation were analyzed.DSRCT most often occurred in young patients (median age, 21.5 years; range, 5-53 years), showing a marked predominance in male patients (86 male patients vs eight female patients). Eighty nine-patients (95%) were white (defined in this study as white or Hispanic), four were African American, and one was of Asian descent. Most patients had symptoms, with abdominal pain noted as the most common symptom. At initial presentation, 85 patients (90%) had multifocal disease, nodular disease, diffuse omental and peritoneal disease, or a combination of these conditions. Thirty-eight patients (40%) had diaphragmatic involvement. Thirty-two patients (34%) had liver metastases, and 49 patients (52%) had retroperitoneal involvement in the form of implants, tumoral extension, or nodal involvement. With regard to thoracic findings, 33 patients (35%) had nodal disease, 17 (18%) had pleural effusions, and only two (2%) had lung metastases at presentation. Twelve patients (13%) had calcified lesions.DSRCT is a rare, multifocal peritoneal malignancy with frequently disseminated abdominal disease at presentation. In the abdomen, disease most commonly involves the omentum and peritoneum, followed by the retroperitoneum. The liver is the most common solid visceral metastatic site. A substantial number of patients have diaphragmatic involvement. In the thorax, nodal and pleural involvement is more common than lung involvement.

Synovial sarcoma (SS) arising within a knee joint is extremely rare, with 10 reported cases in pediatric and adolescent patients in English literature. Its rarity and nonspecific clinical and radiological features pose a diagnostic challenge. We present two cases of primary intra-articular SS of left knee to enhance awareness of this entity. One patient is a 17-year-old male complained of left knee pain and gait abnormality for 9 years. The other one is a 13-year-old female presented with left knee pain for one year. Both cases were clinically diagnosed as benign joint lesion and underwent biopsies. Histological examination, immunohistochemical staining and molecular study confirmed that both patients had primary intra-articular SS, monophasic spindle cell type. Intraarticular SS should be considered as a potential diagnosis with unexplained long-standing knee pain.

Background Staging retroperitoneal lymph node dissection (RPLND) for paratesticular rhabdomyosarcoma (RMS) is recommended for all patients aged ≥10 y. The purpose of this study was to evaluate adherence with surgical resection guidelines for RPLND in patients with paratesticular RMS as a measure for surgical quality. Materials and methods All patients with paratesticular RMS were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2012. Patients were divided into two eras to reflect before (1973-2002) and after (2003-2012) the release and dissemination of the 2001 surgical guidelines for staging ipsilateral RPLND in all patients aged ≥10 y with paratesticular RMS. Survival outcomes associated with lymph node dissection were calculated using the Kaplan–Meier method and Cox proportional hazards analysis. Results Two hundred thirty-five patients with paratesticular RMS were identified and included in the study, among whom 111 were adolescents aged 10-20. RPLND did not significantly increase after 2003 among adolescents (45%-61%, P = 0.09). The benefit of RPLND on improved 5-y overall survival was evident among adolescents (92% versus 64%, P = 0.003). Adjusting for histology, age, stage at diagnosis, and race/ethnicity, RPLND was associated with improved overall survival among patients aged ≥10 y (hazard ratio 0.37, 95% confidence interval 0.17-0.83). Conclusions Despite surgical guidelines recommending RPLND in pediatric patients aged ≥10 y, nearly one-third of adolescent patients did not undergo RPLND. These findings are disturbing considering the survival benefit associated with RPLND among adolescent patients and indicate an opportunity for improvement in surgical quality.

The purpose of this study was to determine whether racial/ethnic disparities exist in disease presentation, treatment, and survival among children and adolescents with extremity sarcoma.The Surveillance, Epidemiology, and End Results (SEER) data were analyzed for patients20years old with soft-tissue extremity sarcomas from 1973 to 2013. Multivariate logistic regression was performed to determine the association between race/ethnicity and disease stage at presentation and likelihood of surgical resection. Overall survival (OS) was evaluated using hazard ratios with 95% confidence intervals.1261 cases were identified: 650 (52%) non-Hispanic whites (NHW), 313 (25%) Hispanics, 182 (14%) non-Hispanic blacks (NHB), and 116 (9%) other race/ethnicity. Logistic regression results showed that Hispanics and NHB were 51% and 44%, respectively, less likely to undergo surgical resection compared to NHW (OR=0.49, 95% CI: 0.30-0.80; OR=0.56, 95% CI: 0.32-0.98, respectively). Factors associated with failure to undergo surgical resection included histology, lower extremity site, tumor size, and distant metastases. OS based on race/ethnicity significantly differed using the log-rank test, with NHB having the worst survival (p0.05).We conclude that NHB, Hispanics, and other race/ethnicity were less likely to undergo surgical resection for extremity sarcoma. Further work is needed to better characterize and eliminate disparities in the management and outcomes of children with extremity sarcomas.Prognosis study.IV.

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable, soft tissue sarcoma subtype that presents with diffuse abdominal sarcomatosis in adolescents and young adults. This article presents the largest retrospective analysis conducted to date of patients with DSRCT who were treated with an anti‐angiogenic therapy., Background. Desmoplastic small round cell tumor (DSRCT) is an aggressive, often fatal soft tissue sarcoma that lacks an optimal salvage regimen. We retrospectively reviewed data from 29 pretreated DSRCT patients who received pazopanib at MD Anderson Cancer Center after failure of standard chemotherapies. Subjects, Materials, and Methods. Medical records of patients treated from January 2012 to December 2016 were reviewed and regression analyses were performed. Median progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan‐Meier method and differences in survival were assessed by a log‐rank test. A landmark statistical analysis was used to assess OS at a predefined 12‐week time point following pazopanib initiation. Results. The mean age at pazopanib treatment was 27.5 years (range, 6.3–50.1 years). According to RECIST 1.1 criteria, 16 patients (55%) had stable disease, 1 patient (3%) had partial response, 1 patient (3%) had complete response, and 11 patients (38%) had progressive disease. Estimated median PFS was 5.63 months (95% confidence interval [CI]: 3.23–7.47). Median OS was 15.7 months (95% CI: 10.3–32.4). As of December 2016, 11 patients (38%) were still alive, with a median follow‐up time of 16.8 (range 3.8–30.1) months. Doses between 400 and 800 mg were included. Pazopanib was well tolerated and 23 (79%) of the patients continued it until progression or death, 4 discontinued because of side effects, and 2 were still on pazopanib at the time of data analysis. Conclusion. In the largest study conducted to date in DSRCT, pazopanib was well tolerated and clinically active in heavily pretreated patients who otherwise lack good treatment options. Implications for Practice. Desmoplastic small round cell tumor (DSRCT) is a rare, extremely aggressive soft tissue sarcoma subtype that most commonly occurs in adolescent and young adult males. No DSRCT‐specific therapies exist, and for lack of a better treatment approach, current therapies have relied upon U.S. Food and Drug Administration‐approved drugs like pazopanib that exhibit clinical activity in other sarcoma subtypes. This article describes the largest experience to date using pazopanib as salvage treatment in heavily pretreated DSRCT patients. Pazopanib was well tolerated and clinically active, surpassing predefined metrics proposed by the European Organization for Research and Treatment of Cancer indicative of "active" sarcoma drugs (5.63 months progression‐free survival [PSF], with 62% of the study population achieving progression‐free survival at 12 weeks).

High rates of patients require readmission to the hospital within 6 months of hematopoietic stem cell transplantation (HSCT). We investigated the relationship between readmission rates and outcomes after HSCT in children, adolescents, and young adults (CAYA).A retrospective analysis of patients (26 years or younger) treated with HSCT was conducted.A chart review of 435 CAYA who underwent HSCT from 2008 to 2015 revealed that 171 patients (39%) had at least 1 hospital readmission within 180 days of transplant; 87% received allogeneic and 13% received autologous HSCT. A total of 312 readmission events were reported. The median follow-up time was 31 months. Documented infection (n=99) and graft-versus-host disease complications (n=60) were the most common causes. Higher than 2 readmission rates were associated with lower overall survival (OS) (P=0.001) and disease-free survival (P0.001) in patients who received allogeneic HSCT. These findings were not found in the autologous HSCT. In a multivariate analysis of those who received allogeneic HSCT, prior treatment with ≥2 chemotherapy regimens (P=0.03) was independent predictor of lower OS. There were also trends noted toward lower OS for patients with documented infections at index admission or subsequent readmissions (P=0.09).More than 2 hospital readmissions within 6 months of allogeneic HSCT in CAYA, who are either heavily pretreated or had documented infections at index admission or subsequent readmissions adversely affected the outcomes.

e15022 Background: Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains only reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety. Methods: Here, we enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients. Results: We discovered the CSV+CTC could serve as a possible biomarker of disease with sensitivity of 85.3% and specificity of 75%. Significantly, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative (773 days vs 2622 days). Addition of readily available genetic analyses improved the sensitivity in both diagnostic and prognostic tests. Conclusions: Our findings indicate that CSV+ CTCs have both diagnostic and prognostic value and can possibly serve as a measure of disease burden.

In this article, we present the case of a 6-year-old female presented to the emergency department with progressive ascending motor weakness leading to cardiac arrest. The recent medical history included neck trauma 1 month prior to admission, 2 weeks of subjective fevers, and 1 day of urinary incontinence. After stabilization, and a review of the recent signs and symptoms, a magnetic resonance imaging of the neck revealed a posterior neck mass from C2 to T2. Neurosurgical removal of the mass was consistent with Ewing's sarcoma. Neck pain is a common presentation in the pediatric population, with the most common cause being traumatic. When coupled with neurological deficits, further studies are warranted to evaluate for organic causes.

BACKGROUND Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older. METHODS Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence. RESULTS This retrospective review of more than 36,000 patients with CRC showed that early-onset patients were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P

Purpose: The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223RaCl2) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers. Patients and Methods: A 3+3 phase I, dose-escalation trial of 223RaCl2 (50, 75, and 100 kBq/kg) was designed in patients with recurrent/metastatic osteosarcoma aged ≥15 years. Objective measurements included changes in standardized uptake values of positron emission tomography (PET; 18FDG and/or NaF-18) and single-photon emission CT/CT (99mTc-MDP) as well as alkaline phosphatase and bone turnover markers at baseline, midstudy, and the end of the study. Results: Among 18 patients enrolled (including 15 males) aged 15–71 years, tumor locations included spine (n = 12, 67%), pelvis (n = 10, 56%), ribs (n = 9, 50%), extremity (n = 7, 39%), and skull (n = 2, 11%). Patients received 1–6 cycles of 223RaCl2; cumulative doses were 6.84-57.81 MBq. NaF PET revealed more sites of metastases than did FDG PET. One patient showed a metabolic response on FDG PET and NaF PET. Four patients had mixed responses, and one patient had a response in a brain metastasis. Bronchopulmonary hemorrhage from Grade 3 thrombocytopenia (N = 1) was a DLT. The median overall survival time was 25 weeks. Conclusions: The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for 223RaCl2 in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies.

Ovarian angiosarcoma is a rare and aggressive vascular tumor, which has a 5-year overall survival of less than 30% for patients with nonmetastatic disease and almost certain death within 1 year for those with metastasis. Here, we briefly review historical approaches to therapy and present a long-term survivor in the case of an 11-year-old female with metastatic ovarian angiosarcoma. This is the second reported case to utilize heated intraperitoneal chemotherapy in the treatment of this disease. Our patient is currently alive and well 3 years after initial diagnosis, significantly longer than any reported case of advanced-stage ovarian angiosarcoma.

Background and purpose Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignancy. We report survival rates and toxicity associated with sequential multimodality treatment including whole abdominopelvic radiation therapy (WART). Material and methods Medical records of 32 patients with DSRCT treated at our institution were reviewed. Patients underwent chemotherapy, cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC), followed by WART with intensity-modulated radiation or volumetric-modulated arc therapy. Results Median overall survival (OS) was 60 months. After 18 months of follow-up, 20 patients (62.5%) had disease recurrence and median disease-free survival (DFS) was 10 months. Median time to extrahepatic abdominal failure was 19.4 months. Factors affecting time to local progression included liver metastases at diagnosis, and an interval of greater than 5.6 months between diagnosis and HIPEC or greater than 2.1 months between HIPEC and WART. None of these factors altered OS. Grade 3 or higher toxicities occurred in 84% of patients. Conclusions WART following chemotherapy, surgical cytoreduction and HIPEC is an aggressive treatment for DSRCT patients and can result in severe side effects. Our median OS of 5 years is favorable compared to prior studies, despite a median DFS of only 10 months, which may be due to improved salvage therapies.

Purpose: Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males. Given its rarity, optimal treatment has not been defined. Experimental Design: We conducted a retrospective study of 187 patients with DSRCT treated at MD Anderson Cancer Center over 2 decades. Univariate and multivariate regression analyses were performed. We determined whether chemotherapy, complete cytoreductive surgery (CCS), hyperthermic intraperitoneal cisplatin (HIPEC), and/or whole abdominal radiation (WART) improve overall survival (OS) in patients with DSRCT. Critically, because our institutional practice limits HIPEC and WART to patients with less extensive, potentially resectable disease that had benefited from neoadjuvant chemotherapy, a time-variant analysis was performed to evaluate those adjunct treatment modalities. Results: The pre-2003 5-year OS rate of 5% has substantially improved to 25% with the advent of newer chemotherapies and better surgical and radiotherapy techniques (HR, 0.47; 95% CI, 0.29–0.75). Chemotherapy response (log rank P = 0.004) and CCS (log rank P < 0.0001) were associated with improved survival. Although WART and HIPEC lacked statistical significance, our study was not powered to detect their potential impact upon OS. Conclusions: Improved 3- and 5-year OS were observed following multidisciplinary treatment that includes Ewing sarcoma (ES)-based chemotherapy and complete tumor cytoreductive surgery, but few if any patients are cured. Prospective randomized studies will be required to prove whether HIPEC or WART are important. In the meantime, chemotherapy and CCS remain the cornerstone of treatment and provide a solid foundation to evaluate new biologically targeted therapies. Clin Cancer Res; 24(19); 4865–73. ©2018 AACR.

Purpose To assess clinical outcomes and patterns of failure, particularly regional nodal control, for pediatric patients treated with proton beam therapy (PBT) for head and neck alveolar rhabdomyosarcoma (HN-ARMS). Materials and Methods Between 2006 and 2015, 14 patients with HN-ARMS were enrolled in a prospective registry protocol and treated with PBT at a single institution. Of the patients, 8 (57%) presented with localized disease and 6 (43%) with regional nodal metastases. All patients were treated with systemic therapy per accepted cooperative group regimens. All patients received PBT to the primary site and involved nodal disease with a median dose of 50.4 Gy (relative biological effectiveness). Elective nodal irradiation was not delivered. Results The median follow-up period for surviving patients was 4.3 years. The 5-year overall survival and disease-free survival rates for the cohort (N = 14) were 45% and 25%, respectively. There were 10 relapses in the cohort: 7 regional nodal, 1 combination local and regional nodal, and 2 leptomeningeal. In 6 of 8 patients (75%) with no nodal disease at diagnosis, isolated regional nodal relapse developed. All nodal relapses occurred in first-echelon draining lymph node basins relative to the primary tumor site. Of 6 patients who presented with nodal metastases, 2 had regional nodal relapse; both of these nodal relapses occurred in the same nodal basin that was initially involved by disease but was not completely targeted as part of the primary treatment plan. Conclusions High rates of regional nodal relapse are observed for HN-ARMS patients, including patients with no nodal disease at diagnosis. These data suggest that HN-ARMS patients may benefit from elective nodal irradiation to treat at-risk draining lymph node stations relative to the primary tumor site. We further recommend coverage of the entire nodal level for any sites of initial nodal disease at diagnosis, given the high risk of failure at these sites.

Cardiotoxic side effects of anthracyclines limit their use as effective chemotherapeutics. One mechanistic model of anthracycline-induced cardiotoxicity is attributed to the generation of intracellular reactive oxygen species (ROS). However, this theory has been questioned because several cardioprotective strategies have included the use of antioxidants without significant clinical benefit. We sought to determine whether measurement of intracellular reactive oxygen species after anthracycline exposure in vivo and in vitro could provide a means for designing more effective antioxidant-based cardioprotective schemes. Intracellular levels of ROS were assessed in peripheral blood mononuclear cells from leukemia bearing mice exposed to anthracyclines and in patients receiving anthracyclines. Comparison of cell death induction and ROS levels were also conducted in vitro in cardiomyocyte and leukemia lines. ROS blockade using antioxidants was conducted, and effects on cell death were assessed. Elevated ROS in blood of mice and representative patient samples correlated with cardiomyocyte necrosis and decreased ejection fraction. In vitro, comparison of the cytotoxic effects of anthracyclines in acute leukemia cells and in cardiomyocytes revealed distinct kinetics of cell death induction and dependence upon oxidative stress. Although apoptotic cell death was observed in both acute leukemia cells and cardiomyocytes, the antioxidant N-acetylcysteine protected cardiomyocytes but not acute leukemia cells from anthracycline cytotoxicity. Our findings point toward revisiting the use of NAC as a cardioprotective agent since it does not appear to interfere with the cytotoxic action of anthracyclines. NAC has been evaluated clinically for cardioprotective activity but future trials must ensure that adequate dose, scheduling and incorporation of markers of oxidative stress are included.

BACKGROUND Pediatric neuroendocrine tumors (NETs) are rare tumors. The purpose of this study is to report the clinical characteristics and outcomes of pediatric patients treated for NET at a single institution. PROCEDURE A retrospective record review. RESULTS There were 33 evaluable patients with median age of 17.9 years (range, 9.9 to 21.9 y) and predominantly females (58%). There were 17 patients with well-differentiated appendiceal NET, whereas 16 were nonappendiceal. Most common nonappendiceal sites were unknown primary (N=6) and pancreas (N=4). Majority of tumors were low grade (N=24, 73%) and small (T1, N=22, 67%). Nonappendiceal tumors were more likely to be larger or high-grade tumors (5/16, 31%), or with metastasis. All appendiceal NET patients underwent curative surgery. All patients who experienced treatment failure had nonappendiceal NET, despite prior chemotherapy in 8 of 9 patients. The 5-year overall survival rates for patients with appendiceal and nonappendiceal NET were 100% and 66% (95% CI, 45%-95%; P=0.006); and 5-year relapse-free survival rate for patients with appendiceal and nonappendiceal NET were 100% and 41% (95% CI, 22%-75%; P=0.002). CONCLUSIONS Well-differentiated appendiceal tumors were the most common pediatric NET and have an excellent prognosis. Better therapies are needed for patients with nonappendiceal NET.

BACKGROUND: Among colorectal carcinoma patients, approximately 150 patients/year are age 25 years old or younger according to Surveillance, Epidemiology, and End Results Program statistics. Because of lack of screening in their age group, they are at risk to have more advanced disease and have been largely unstudied. OBJECTIVE: To determine outcome of colon cancer adolescent and young adult patients. METHODS: Patients under the age of 26 were retrospectively reviewed from a single institution. RESULTS: The 5-year overall survival rate from the time of the first surgery was .45 (95% confidence interval .17 to .70). The median overall survival for the cohort was 2.98 years. Patients aged 15 to 21 years had a poorer overall survival than patients aged 22 to 25 years (82% survival vs 100% at 2 years and zero vs 56% at 5 years). Five patients underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Three are alive at 82, 36, and 16 weeks after hyperthermic intraperitoneal chemotherapy. CONCLUSIONS: Patients less than 21 years with nonsyndromic colorectal carcinoma may have a poorer outcome. Novel, more aggressive therapy may be necessary in these patients.

Pediatric malignancies in adults, in contrast to the same diseases in children are clinically more aggressive, resistant to chemotherapeutics, and carry a higher risk of relapse. Molecular profiling of tumor sample using next generation sequencing (NGS) has recently become clinically available. We report the results of targeted exome sequencing of six adult patients with pediatric-type malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and desmoplastic small round cell tumor (n=1) with a median age of 28.8 years. Detection of druggable somatic aberrations in tumors is feasible. However, identification of actionable target therapies in these rare adult patients with pediatric-type malignancies is challenging. Continuous efforts to establish a rare disease registry are warranted.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma that primarily affects adolescents and young adults. Patients can present with many peritoneal implants. We conducted a Phase II clinical trial utilizing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) with Cisplatin for DSRCT and pediatric type abdominal sarcomas. METHODS: A prospective cohort study was performed on 20 patients, who underwent CRS-HIPEC procedures, with Cisplatin from 2012–2013. All patients were enrolled in the phase 2 clinical trial. Patients with extra-abdominal disease and in whom a complete cytoreduction (CCR0-1) could not be achieved were excluded. All outcomes were recorded. RESULTS: Fourteen patients had DSRCT while 5 patients had other sarcomas. One patient had repeat HIPEC. Patients with DSRCT had a significantly longer median overall survival after surgery than patients with other tumors (44.3 months vs. 12.5 months, p = 0.0013). The 3-year overall survival from time of diagnosis for DSRCT patients was 79%. The estimated median recurrence-free survival (RFS) was 14.0 months. However, RFS for patients with DSRCT was significantly longer than for non-DSRCT patients (14.9 months vs. 4.5 months, p = 0.0012). Among DSRCT patients, those without hepatic or portal metastases had a longer median RFS than those with tumors at these sites (37.9 months vs. 14.3 months, p = 0.02). In 100% of patients without hepatic or portal metastasis, there was no peritoneal disease recurrence after CRS-HIPEC. CONCLUSIONS: Complete CRS-HIPEC with Cisplatin is effective in select DSRCT patients. DSRCT patients with hepatic or portal metastasis have poorer outcomes.

Background To determine whether there are racial/ethnic disparities in disease presentation, treatment and survival outcomes among children and young adults with chest wall sarcomas. Methods The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients 21 years old and younger with chest wall sarcoma. We performed multivariate logistic regression to investigate the association of race/ethnicity with advanced stage of disease at presentation and likelihood of undergoing surgical resection. Overall survival (OS) was evaluated using Cox regression modeling to calculate hazard ratios with 95% confidence intervals. Results A total of 669 patients were identified: 393 non-Hispanic whites (NHW) (59%), 151 Hispanics (23%), 64 non-Hispanic blacks (NHB) (11%), and 64 other race/ethnicity (9%). The 5- and 10-year OS rates for the entire cohort were 69% and 64%, respectively. NHB had significantly worse 5-year and 10-year OS compared to NHW based on the log rank test (61% versus 70%, 52% versus 66%, respectively; p = 0.037).). Most patients (80%) underwent surgical resection. However, NHB were less likely than NHW to undergo surgical resection by multivariate analysis (OR 0.43, 95% CI 0.22–0.82). Conclusions NHB children and young adults with chest wall sarcoma have decreased overall survival. In addition, NHB are less likely to undergo surgical resection which may contribute to survival disparities. It is paramount that health care providers work to close the treatment gap between racial/ethnic groups to improve survival in children and young adults with chest wall sarcoma. Level of evidence Level III Treatment Study.

Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4–14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7–16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).

Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT).We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis.Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09).Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Granulosa cell tumors (GCTs) of the testis are rare testicular neoplasms and are clinically divided into two subgroups, adult-type (AGCT) and juvenile-type (JGCT). AGCTs typically occur in the mid-fifth decade of life, while JGCTs almost always occur in males less than one year of age. A painless scrotal mass is the most common presentation, but testicular torsion and retroperitoneal lymphadenopathy is encountered in up to 20% of AGCT cases. Some JGCT cases have presented in patients with X/XY mosaicism and ambiguous genitalia. Surgical resection is the mainstay of therapy, and the majority of patients have a good prognosis. The role of chemotherapy and radiation therapy in metastatic patients remains unclear.

Background Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by ASPL-TFE3 translocation. Apart from complete surgical resection, there is no standard management strategy. Procedure The clinical data of 69 children and young adults less than 30 years old with ASPS diagnosed from 1980-2014 were retrospectively collected from four major institutions. Results Median age at diagnosis was 17 years (range: 1.5-30). Forty-four (64%) were female. Median follow-up was 46 months (range: 1-409). Most common primary sites were limbs (58%) and trunk (24%). ASPL-TFE3 translocation was present in all 26 patients tested. IRS postsurgical staging was I in 19 (28%), II in 7 (10%), III in 5 (7%), and IV in 38 (55%) patients. The 5-year event-free survival (EFS) and overall survival (OS) were 38% and 72%, respectively. The 5-year EFS and OS were 80% and 87%, respectively, for the 31 patients with localized tumors (IRS-I-II-III), and 7% and 61%, respectively, for the 38 patients with metastatic tumors (IRS-IV). Of 11 IRS-IV patients who received targeted therapy upfront, two had partial response, six had stable disease, and three had progressive disease. Median time to progression for IRS-IV patients was 12 months for those treated with targeted therapy, 7 months for cytotoxic chemotherapy (N = 15), and 4 months for observation only (N = 6). Conclusion Localized ASPS has a good prognosis after gross total resection. ASPS is resistant to cytotoxic chemotherapy. Although there are no curative therapies for patients with metastatic disease, prolonged disease stabilization may be achieved with targeted therapies.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used in adults with ovarian carcinoma proving overall survival benefit in randomized trials, but measured in months. Diffuse peritoneal disease from pediatric type ovarian tumors is rare. We applied CRS and HIPEC to pediatric girls with diffuse peritoneal disease as part of a clinical trial. In all patients complete cytoreduction was followed by HIPEC using 100 mg/m2 of cisplatin for 90 min in a closed technique. All received neoadjuvant chemotherapy. Patients with disease outside of the abdominal cavity were excluded. Of 101 pediatric CRS and HIPEC operations, 8 had ovarian primary tumors and multifocal peritoneal disease. There were three yolk sac tumors (germ cell, mixed teratoma), one Sertoli–Leydig, one PNET of the ovary, one choriocarcinoma, one juvenile granulosa cell tumor and one adenocarcinoma. Age ranged 4–18 years. Three of the 8 (37 %) recurred and died. The remaining 63 % are disease free 2–6 years post HIPEC. Overall survival and relapse-free survival in this cohort was 64 and 62 %, respectively [CI 0.64 (0.34, 1); 0.62 (0.37, 1)]. This is the first report of CRS and HIPEC in pediatric ovarian tumors. HIPEC may be effective in pediatric-type ovarian tumors. More study is needed in a larger cohort.

We evaluated acute toxicity profiles and dosimetric data for children with salivary gland tumors treated with adjuvant photon/electron-based radiation therapy (X/E RT) or proton therapy (PRT).We identified 24 patients who had received adjuvant radiotherapy for salivary gland tumors. Data were extracted from the medical records and the treatment planning systems. Toxicity was scored according to the Common Terminology Criteria for Adverse Effects 4.0.Eleven patients received X/E RT and 13 PRT, with a median prescribed dose of 60 Gy in each group. In the X/E RT group, 54% of patients developed acute grade II/III dermatitis, 27% grade II/III dysphagia, and 91% grade II/III mucositis, and the median weight loss was 5.3% with one patient requiring feeding tube placement. In the PRT group, 53% had acute grade II/III dermatitis, 0% grade II/III dysphagia, and 46% grade II/III mucositis, with a median weight gain of 1.2%. Additionally, PRT was associated with lower mean doses to several normal surrounding midline and contralateral structures.In this retrospective study of pediatric salivary tumors, PRT was associated with a favorable acute toxicity and dosimetric profile. Continued follow-up is needed to identify long-term toxicity and survival data.

Purpose: To determine whether there are racial/ethnic disparities in disease presentation and survival outcomes among children and young adults with chest wall sarcomas. Methods: The Surveillance, Epidemiology and End Results (SEER) database from 1973-2013 was analyzed for all patients less than 24 years old and diagnosed with chest wall based on primary tumor histology and primary tumor site. Tumor histology was categorized as skeletal for histologic subtypes arising from bone and extra-skeletal for histologic subtypes arising from soft tissues. Tumor sites included thorax, clavicle, sternum and ribs. We performed multivariate logistic regression to investigate the association of race/ethnicity with advanced stage of disease at presentation and likelihood of undergoing surgical resection after adjusting for age, sex, treatment, tumor size and sarcoma type. Overall survival (OS) was evaluated using Cox regression to estimate hazard ratios with 95% confidence intervals. All statistics were calculated with SPSS Statistics Version 23. Results: A total of 598 patients were identified and included 363 non-Hispanic whites (61%), 129 Hispanics (22%), 57 non-Hispanic blacks (10%), and 49 other race/ethnicity (8%). The mean age at diagnosis was 14 + 6.6 years. Most patients presented with advanced stage disease defined as regional or distant disease (393, 66%). Race/ethnicity was not associated with stage of disease at presentation. However, patients with advanced stage disease were more likely to have a skeletal sarcoma (OR= 2.55, 95% CI: 1.71-3.80), tumor size ≥8 cm (OR= 3.66, 95% CI: 2.35-5.71) and undergone radiation therapy (OR= 1.80, 95% CI: 1.22-2.67). Those who underwent surgical resection were less likely to present with advanced disease (OR=0.34; 95% CI: 0.20-0.59). The 5- and 10-year OS for the entire cohort were 62% and 58%, respectively. Non-Hispanic blacks had a worse 5-year and 10-year OS compared to Non-Hispanic whites (54% versus 65%, 48% versus 60%, respectively). In the univariate analysis, non-Hispanic Blacks were 63% more likely to die than non-Hispanic whites (95% CI 1.07-2.49); however, this association was mitigated after controlling for age at diagnosis, sex, tumor type, tumor size, disease stage, surgical resection and radiation treatment in the multivariate analysis. In the multivariate analysis, predictors of worse OS included older age at diagnosis (HR 1.05, 95% CI 1.03-1.07), tumor size > 8cm (HR 2.15, 95% CI 1.50-3.10), regional disease (HR 1.79, 95% CI 1.19-2.69), distant disease (HR 3.99, 95% CI 2.67-5.96), and failure to undergo surgical resection (HR 2.08, 95% CI 1.55-2.81). Most patients (79%) underwent surgical resection. However, non-Hispanic blacks were less likely than non-Hispanic whites to undergo surgical resection even after controlling for sex, age at diagnosis, tumor type, tumor size, disease stage, and radiation therapy (OR 0.49, 95% CI 0.25-0.97). Conclusions: Non-Hispanic black children and young adults with chest wall sarcomas have decreased overall survival compared to non-Hispanic whites. In addition, Non-Hispanic blacks are less likely to undergo surgical resection of their tumors which may contribute to the survival disparities identified in this study. Citation Format: Michael Joseph, Emma Hamilton, Winston Huh, Andrea Hayes-Jordan, Mary Austin. The impact of racial/ethnic disparities on survival for children and young adults with chest wall sarcoma: A population-based study. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C47.

Aim Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). Methods We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. Results Forty-two patients were identified. Median age was 6.4 years (range 0.6–9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7–29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53–84%) and 82% (95% CI: 71–95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09). Conclusion Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Background Staging retroperitoneal lymph node dissection (RPLND) for paratesticular rhabdomyosarcoma (RMS) is recommended for all patients aged ≥10 y. The purpose of this study was to evaluate adherence with surgical resection guidelines for RPLND in patients with paratesticular RMS as a measure for surgical quality. Materials and methods All patients with paratesticular RMS were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2012. Patients were divided into two eras to reflect before (1973-2002) and after (2003-2012) the release and dissemination of the 2001 surgical guidelines for staging ipsilateral RPLND in all patients aged ≥10 y with paratesticular RMS. Survival outcomes associated with lymph node dissection were calculated using the Kaplan–Meier method and Cox proportional hazards analysis. Results Two hundred thirty-five patients with paratesticular RMS were identified and included in the study, among whom 111 were adolescents aged 10-20. RPLND did not significantly increase after 2003 among adolescents (45%-61%, P = 0.09). The benefit of RPLND on improved 5-y overall survival was evident among adolescents (92% versus 64%, P = 0.003). Adjusting for histology, age, stage at diagnosis, and race/ethnicity, RPLND was associated with improved overall survival among patients aged ≥10 y (hazard ratio 0.37, 95% confidence interval 0.17-0.83). Conclusions Despite surgical guidelines recommending RPLND in pediatric patients aged ≥10 y, nearly one-third of adolescent patients did not undergo RPLND. These findings are disturbing considering the survival benefit associated with RPLND among adolescent patients and indicate an opportunity for improvement in surgical quality.

11029Background: Radium-223 dichloride (223RaCl2 ) is an alpha-emitting radiopharmaceutical and calcimimetic that has intrinsic bone-targeting properties. It is now approved for bone metastases fro...

11069Background: ARMS is considered to be one of the most aggressive pediatric malignancies. Adults with ARMS notoriously experience inferior outcomes. Our goal was to define our adult population w...

Background: Early phase clinical trials are often limited to adults, reducing the opportunity to explore safety and efficacy of new agents in children. Pre-clinical models have shown that combining an mTOR inhibitor (everolimus) with a multikinase VEGFR2 inhibitor (vandetanib) overcomes intrinsic and /or acquired resistance to either agent alone. Since this combination may have activity against pediatric cancer, pediatric patients were eligible for enrollment (NCT01582191). Methods: We designed a conventional 3+3 Phase I study to determine the safety, maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and dose-limiting toxicities (DLTs) of this combination using oral vandetanib and oral everolimus in pediatric patients with advanced solid tumors. Younger patients were enrolled at the accruing dose level, with BSA-based dose adjustments for smaller children. Tumor responses were assessed using RECIST v1.1. Results: To date, 15 pediatric patients were enrolled between February 2013 and May 2015. The median age was 18 years (range 8-26 years) and 8 patients (53%) were male. The most common diagnosis was sarcoma (n=9; 5 soft tissue and 4 bone). Seven patients (47%) had 2 or more sites of metastases. One patient was treated at dose level 0 (vandetanib 100 mg daily + everolimus 2.5 mg daily), another at dose level 1 (vandetanib 200 mg daily + everolimus 2.5 mg daily), and 13 patients at dose level 4 (determined to be the MTD, vandetanib 300 mg daily + everolimus 10 mg daily). The most common adverse events observed in patients across different dose levels included G1 rash (n=4); G1 fatigue (n=2); G1-G2 hypertension (n=2); G1-G2 QTc prolongation (n=2); G1-G4 transaminitis (n=4); G1-G4 thrombocytopenia (n=3). Eight patients (53%) were taken off study due to disease progression and one patient (7%) due to drug toxicity. One patient with epithelioid sarcoma had a PR (74% tumor size reduction) and one patient with AKT1 p.E17K mutant pseudopapillary pancreatic tumor had a 15% reduction in tumor size. In addition, two patients with alveolar soft part sarcoma had stable disease with clinical benefit. Conclusions: The toxicities of the combination of everolimus with vandetanib seen in children are similar to those seen in adults. Evidence of response was noted in heavily pre-treated pediatric patients with refractory solid tumors. Including younger patients in institutional phase I trials provides a mechanism to study new combinations in children. Note: This abstract was not presented at the conference. Citation Format: Hatel Rana Moonat, Michael Roxas, Winston W. Huh, Cynthia E. Herzog, Sarina Piha-Paul, Najat C. Daw, Michael Rytting, Estella Mote, Erica N. Ward, Yazan Amin, Funda Meric-Bernstam, Cindy L. Schwartz, Vivek Subbiah. Phase I study of Everolimus (mTOR inhibitor) in combination with Vandetanib (multikinase inhibitor of EGFR,VEGFR,RET) in children, adolescents, and young adults with advanced solid tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A48.