Non-rhabdomyosarcoma Soft Tissue Sarcomas Research Articles

Improved Survival of Children, Adolescents, and Young Adults With Head and Neck Soft Tissue Sarcomas in Denmark.

The aim of this study was to estimate nationally the survival of children, adolescents, and young adults with head and neck soft tissue sarcomas. The authors included patients 0 to 21 years of age and diagnosed with rhabdomyosarcoma (RMS) or nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) located in the head and neck between 1980 and 2014. Survival probabilities were estimated using the Kaplan-Meier method. The authors estimated the effect of covariates with univariate and multivariate Cox regression analyses. The cumulative recurrence in RMS was estimated when considering death as a competing risk. We identified 72 patients (50% male individuals, whereas 72% had RMS). Elder patients (older than 15 y) did worse compared with younger patients (log-rank test P=0.001). Patients diagnosed from 1980 to 1999 did worse than patients diagnosed from 2000 to 2014 (log-rank test P=0.02). Similarly, younger (younger than 15 y) patients did significantly better when diagnosed from 2000 to 2014 with reference to those diagnosed from 1980 to 1999 (log-rank test P=0.026). The multivariate hazard ratio was 0.46 (95% confidence interval, 0.23-0.92) for patients diagnosed from 2000 to 2014 with reference to patients diagnosed from 1980 to 1999. The 1-year cumulative recurrence for RMS was 21.2% (95% confidence interval, 12.3%-35.0%). Overall survival has improved throughout the study period, which is attributable to advancement in diagnostics, treatment, and the application of standardized guidelines from international protocols.

Overview of the clinical and imaging features of the most common non-rhabdomyosarcoma soft-tissue sarcomas.

Non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS) refers to a widely heterogeneous group of extraskeletal mesenchymal neoplasms accounting for approximately 4% of all childhood cancers. This article summarizes the clinical and imaging features of these rare tumors and describes in detail the three most common histological types of NRSTSs encountered in children - synovial sarcoma, malignant peripheral nerve sheath tumor and infantile fibrosarcoma. The author discusses the role of non-cross-sectional and cross-sectional imaging.

Exosomal MiRNAs in Pediatric Cancers.

MicroRNAs (miRNAs) have generated great attention in oncology as they play a fundamental role in the regulation of gene expression and their aberrant expression is present in almost all types of tumors including pediatric ones. The discovery that miRNAs can be transported by exosomes, which are vesicles of 40–120 nm involved in cellular communication, that are produced by different cell types, and that are present in different biological fluids, has opened the possibility of using exosomal miRNAs as biomarkers. The possibility to diagnose and monitor the progression and response to drugs through molecules that can be easily isolated from biological fluids represents a particularly important aspect in the pediatric context where invasive techniques are often used. In recent years, the idea of liquid biopsy as well as studies on the possible role of exosomal miRNAs as biomarkers have developed greatly. In this review, we report an overview of all the evidences acquired in recent years on the identification of exosomal microRNAs with biomarker potential in pediatric cancers. We discuss the following herein: neuroblastoma, hepatoblastoma, sarcomas (osteosarcoma, Ewing’s sarcoma and rhabdoid tumors, and non-rhabdomyosarcoma soft tissue sarcoma), brain tumors, lymphomas, and leukemias.

Effect of Peri-Operative Radiotherapy Boost on Local Control in Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma (NSTS)

Effect of Peri-Operative Radiotherapy Boost on Local Control in Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma (NSTS)

Results of the dose-finding phase of ARST 1321 from the Children's Oncology Group and NRG Oncology: Neoadjuvant chemoradiation or radiation therapy +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcomas.

11070 Background: Pazopanib is a tyrosine kinase inhibitor approved globally for advanced soft tissue sarcomas. The dose finding phase of this cooperative group trial assessed the dose limiting toxicities (DLT) and the maximally tolerated dose (MTD) of adding pazopanib to neoadjuvant chemoradiation or radiation therapy in children and adults with unresected intermediate/high-risk trunk and extremity non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Methods: ARST1321, a jointly designed intergroup study lead by Children's Oncology Group and NRG Oncology opened for enrollment in July 2014. Eligible adult and pediatric patients with newly diagnosed, unresected trunk/extremity NRSTS with plans for primary tumor resection were enrolled into either the Chemotherapy Cohort (those with chemosensitive NRSTS > 5 cm, grade 3, including all synovial sarcoma) or the Non-Chemotherapy Cohort (those with chemotherapy insensitive NRSTS of any size, grade 2/3, or any chemosensitive NRSTS for whom no chemotherapy was planned per discretion of patients and treatment teams). In the Chemotherapy Cohort, pazopanib was given with ifosfamide (7.5 grams/m2) and doxorubicin (75 mg/m2) plus 45 Gy preoperative RT starting after cycle 2. Primary tumor was resected at week 13, followed by chemotherapy and pazopanib to week 25. In the Non-Chemotherapy Cohort, pazopanib was given with 50 Gy preoperative RT, primary tumor was resected at week 10, and pazopanib continued to week 25. Feasibility was assessed through week 6 of therapy to determine pazopanib dose escalation/de-escalation based on DLT, total doses of pazopanib, and overall adverse event profile. Results: In the Chemotherapy Cohort, MTD was reached at Dose Level 1 (350 mg/m2 peds; 600 mg adults) with two DLTs (1 grade 3 ALT rise, 1 intolerability to therapy) in 10 patients. In the Non-Chemotherapy Cohort, 11 patients enrolled at Dose Level 1 (350 mg/m2 peds; 600 mg adults) without any observed DLTs and all received ≥75% of prescribed total pazopanib dose; MTD was reached at Dose Level 2 (450 mg/m2 peds; 800 mg adults) with 2 DLTs in ten patients enrolled (1 grade 3 dermatitis and 1 intolerability to therapy) and 9/10 receiving ≥75% of full dose. Conclusions: Pazopanib in combination with chemoradiation or radiation therapy alone was found to be safe in children and adults with NRSTS. Following this finding, ARST1321 opened in both arms using the newly determined pazopanib MTDs. Clinical trial information: NCT02180867.

Preoperative chemoradiation +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology.

11002 Background: Pazopanib is a multi-targeted tyrosine kinase inhibitor with activity in advanced soft tissue sarcoma. ARST1321 is a phase II study designed to compare the near complete pathologic response rate (≥ 90% necrosis) of preoperative chemoradiation +/- pazopanib in children and adults with intermediate/high risk chemotherapy-sensitive NRSTS. Methods: ARST1321 is a jointly designed COG and NRG Oncology study opened to enrollment in July 2014. Eligible adult (≥18 years) and pediatric ( < 18 years) patients with unresected, newly diagnosed truncal/extremity NRSTS were enrolled into the Chemotherapy Cohort ( > 5 cm, grade 2/3, protocol-designated chemotherapy-sensitive histology). Following a dose-finding phase, patients were randomized to receive (Regimen A) or not receive (Regimen B) pazopanib ( < 18 years: 350 mg/m2/day; ≥ 18 years: 600 mg/day) in combination with ifosfamide (7.5 gm/m2/cycle) and doxorubicin (75 mg/m2/cycle) + 45 Gy preoperative RT followed by primary resection at week 13, then adjuvant chemotherapy. Results: As of June 30, 2018, 81 eligible patients were enrolled and randomized. Week 13 response is available for 42 patients (60% of expected information). The rate of ≥ 90% pathologic necrosis was 58.3% for Regimen A and 22.2% for Regimen B. Based on the significance level of 0.081 (for the second efficacy analysis with overall one-sided significance level of 0.20, power of 0.80, and O’Brien-Fleming-type cumulative error spending function), the 83.8% confidence interval for the difference was between 16.5% and 55.8%. At this predetermined interim analysis, the efficacy bound was crossed indicating that Regimen A is more efficacious than Regimen B. Given these findings, enrollment was stopped. Grade 3/4 toxicities were 73.8% for Regimen A and 29% for Regimen B with neutropenia, thrombocytopenia and febrile neutropenia being the most common toxicities. Conclusions: The rate of near complete pathologic response was significantly greater with the addition of pazopanib to preoperative chemoradiation in children and adults with intermediate/high risk NRSTS. The comparison of survival outcomes requires longer follow-up. Clinical trial information: NCT02180867.

Does the addition of chemotherapy to neoadjuvant radiotherapy impact survival in high-risk extremity and trunk soft tissue sarcoma?

11054 Background: Large, high-grade extremity/trunk (ET) non-rhabdomyosarcoma soft-tissue sarcoma (STS) is at high risk for distant recurrence and death. The integration of chemotherapy (C) to standard of care neoadjuvant radiotherapy (RT) remains controversial, even for these patients. This study examines the impact of adding C to neoadjuvant RT on overall survival (OS) in high risk ET-STS. Methods: The National Cancer Data Base (NCDB) was queried for patients ≥18 years with high risk (≥5 cm + high grade) non-rhabdomyosarcoma ET-STS (WHO histology) who received neoadjuvant RT and limb sparing surgery from 2006-2014. Patients were next stratified based upon receipt of C (RT and CRT cohorts). Overall survival (OS) for RT vs CRT cohorts was analyzed using the Kaplan-Meier (KM) method, log-rank test, and Cox proportional hazards models. Propensity score-matched analysis (PSM) was employed to account for potential treatment selection bias between cohorts. Results: A total of 848 (71.1%) and 344 (28.9%) patients received RT and CRT, respectively. Patient cohorts were well-balanced except for the CRT cohort having higher rates of treatment in the West (22.1% vs 10.6%) & Midwest (28.3% vs 22.7%), Charlson-Deyo [CD] score 0 vs ≥1 (85.5% vs 79.4%), younger age (≤50) (45.9% vs 21.7%), synovial sarcoma histology (18.9% vs 3.2%), earlier year of diagnosis (2006-2010) (39.5% vs 32.3%), and positive lymphovascular invasion (2.0 vs 1.51%), (p < 0.05 each). The KM 5-year OS was significantly higher in the CRT vs RT cohort: 69.2% vs 58.1% on univariate (p < 0.0001) and multivariate analysis (Hazard Ratio [HR]: 0.66; 95% Confidence Interval [CI]: 0.52-0.85; p = 0.001) even after adjusting for age, race, income, CD score, histology, tumor size, tumor grade, and primary site (lower extremity; upper extremity; trunk). PSM identified evenly matched cohorts of 300 patients each with respect to age, income, CD score, histology, grade, tumor size, and primary site. The addition of neoadjuvant C remained prognostic for OS on PSM (HR: 0.74 [0.56-0.99], p = 0.042). Conclusions: The addition of C to neoadjuvant RT was associated with improved OS in patients with high risk non-rhabdomyosarcoma ET-STS in the NCDB. These hypothesis generating results support prospective evaluation.

Sarcoma sinovial de membrana interósea en paciente adolescente. A propósito de un caso

Synovial sarcoma is a malignant mesenchymal neoplasm with variable epithelial differentiation. It can be classified within the group of non-rhabdomyosarcomatous soft tissue sarcomas. It occurs predominantly in lower extremities. The objective is to present an unusual case and to communicate the behavior of this type of cancer. This case is about a 14-year-old female with history of 2 years of progressive pain in the middle third of her right leg; accompanied by a 2 cm palpable mass in the anterolateral region, without inflammatory changes. Computerized tomography reported a tumor of irregular borders involving the peroneal cortical and interosseous membrane. An open biopsy was performed. Histological examination revealed a monophasic synovial sarcoma (Grade 2). The patient received chemotherapy with good response to treatment and with no evidence of recurrence after 4 months.

Lymph Node Sampling and Survival in Child and Adolescent Extremity Soft-Tissue Sarcoma

BackgroundThe significance of lymph node sampling (LNS) on disease-specific survival (DSS) of extremity soft tissue sarcomas (STS) is unknown. We investigated the effect of LNS on DSS in child and adolescent extremity STS. Materials and methodsThe Surveillance, Epidemiology, and End Results registry was queried for patients aged <20 y with extremity STS who underwent surgery. Patient demographics were collected and analyzed. ResultsA total of 1550 patients were included, with findings of 10-y DSS of 74% for all extremity STS and 49% for rhabdoymyosarcoma (RMS) (P < 0.005). LNS was associated with worse DSS in patients with extremity nonrhabdomyosacrcoma soft tissue sarcomas (79% versus 84%, P = 0.036). Conversely, LNS was associated with an improved DSS in patients with extremity RMS (64% versus 49%, P = 0.005). ConclusionsLNS is positively associated with an improved DSS in child and adolescent extremity RMS. Multivariate analysis found no correlation between DSS and LNS in child and adolescent extremity nonrhabdomyosarcoma soft tissue sarcomas.

An update in the management of pediatric sarcoma.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) is a rare subgroup of malignancy in childhood that is composed of a variety of soft tissue and bony tumors. Prognosis for resectable localized disease is usually good and improved with systemic treatment. However, survival from locally advanced and metastatic disease remains poor. There have been numerous preclinical and clinical studies to define histopathology, biology, and genetic alteration of sarcomas. The purpose of this review is to clarify the progress in the management of NRSTS. Genomic analysis, including the use of next-generation sequencing, has revealed fusion transcripts or specific genetic alterations which provide diagnostic biomarkers and potential targets for novel therapies. Most cases are sporadic, but some are associated with genetic predispositions. Most present as a painless mass and diagnosis is frequently delayed because of a low index of suspicion. There is a wide array of histopathological subtypes. Investigations usually involve core, incisional or excisional biopsy for tissue diagnosis, and cross-sectional and nuclear imaging for staging. Management of pediatric sarcoma is largely dependent on the patient's histopathological diagnosis, age, disease stage, and co-morbidities but usually involves a combination of systemic and local therapies. Preclinical studies and phase I/II trials of newer targeted therapies are ongoing.

Non-rhabdomyosarcoma soft tissue sarcoma in a neonate, a rare and aggressive disease: case report

Neonatal soft tissue sarcomas are a rare group of tumors. The behavior and aggressiveness of neonatal STS is variable. Surgical excision has been noted to be most important factor affecting outcome. However, when non-mutilating surgery is not possible, or resection is incomplete, chemotherapy and radiotherapy have been tried with variable success. We encountered a case of a neonate having large soft tissue mass at anterior abdominal wall. Biopsy and immunohistochemistry confirmed it as undifferentiated soft tissue sarcoma. Surgical excision was incomplete with margin positivity. His disease showed recurrence in short duration of time and despite adjuvant chemotherapy, progression was noted. The child abandoned the treatment and died within 3 months of life.

Analysis of mutations in primary and metastatic synovial sarcoma.

Synovial sarcoma is the most common pediatric non-rhabdomyosarcoma soft tissue sarcoma and accounts for about 8–10% of all soft tissue sarcoma in childhood and adolescence. The presence of a chromosomal translocation-associated SS18-SSX-fusion gene is causally linked to development of primary synovial sarcoma. Metastases occur in approximately 50–70% of synovial sarcoma cases with yet unknown mechanisms, which led to about 70–80% mortality rate in five years. To explore the possibilities to investigate metastatic mechanisms of synovial sarcoma, we carried out the first genome-wide search for potential genetic biomarkers and drivers associated with metastasis by comparative mutational profiling of 18 synovial sarcoma samples isolated from four patients carrying the primary tumors and another four patients carrying the metastatic tumors through whole exome sequencing. Selected from the candidates yielded from this effort, we examined the effect of the multiple missense mutations of ADAM17, which were identified solely in metastatic synovial sarcoma. The mutant alleles as well as the wild-type control were expressed in the mammalian cells harboring the SS18-SSX1 fusion gene. The ADAM17-P729H mutation was shown to enhance cell migration, a phenotype associated with metastasis. Therefore, like ADAM17-P729H, other mutations we identified solely in metastatic synovial sarcoma may also have the potential to serve as an entry point for unraveling the metastatic mechanisms of synovial sarcoma.

Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332

For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique. Of 550 eligible patients <30years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique. Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P=.920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P=.011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P=.005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P=.018). Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whetherthese dosimetric findings produce differences in clinical and toxicity outcomes.

Improved survival in AYAs with NRSTS treated at specialized cancer centers in California.

e23551 Background: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of soft tissue tumors whose management benefits from a multidisciplinary therapeutic approach, especially for patients with metastatic or unresectable disease. Published data suggest that cancer treatment at a specialized cancer center (SCC) can mitigate poor outcomes for other cancers. Therefore, we examined the impact of location of treatment, sociodemographic and clinical factors on survival in adolescents and young adults (AYAs) with NRSTS. Methods: We performed a retrospective, population-based analysis of patients (ages 15-39) hospitalized within one year of diagnosis with first primary NRSTS between 2000–2014 using the California Cancer Registry linked with state hospitalization data. Patients were divided into two groups based on receiving all inpatient treatment at a SCC (Children’s Oncology Group and/or National Cancer Institute-designated center) versus part/none. Multivariable Cox proportional hazards regression identified factors associated with overall and sarcoma-specific survival. Kaplan Meier survival analysis was stratified by location of treatment. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Of the 1532 AYA patients with NRSTS, 40.4% percent received all their inpatient care at a SCC. Kaplan Meier analysis demonstrated a higher 5-year survival in patients who received all (vs part/none) care at a SCC (60.0% vs 51.8%; p = 0.0002). Multivariable analysis found that having all treatment at a SCC was associated with significantly better overall (HR 0.81, CI 0.68-0.96) and sarcoma-specific (HR 0.73, CI 0.58-0.92) survival. In addition, inferior survival was associated with African American race/ethnicity, nerve sheath tumor, tumor size > 5 cm, non-localized disease, comorbidities and body wall/visceral tumor location (vs extremity). Conclusions: Our findings demonstrate that treatment for NRSTS at a SCC independently predicts better survival in AYAs and confirms other known predictors of outcomes in this patient population. Eliminating barriers to treatment of AYAs with NRSTS at SCCs could improve survival.

Risk group accurately predicts outcome in primary extremity non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) in patients &lt;30 years of age: Findings from Children’s Oncology Group study ARST0332.

10546Background: Data are limited on primary extremity NRSTS in pediatric patients. Methods: This ARST0332 subset analysis evaluated the clinical features and outcomes of extremity (including shoul...

Visceral primary non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in patients &lt; 30 years of age: Findings of Children’s Oncology Group (COG) study ARST0332.

10545Background: Little is known about the clinical features, optimal management, and prognosis of young patients with primary visceral NRSTS. Methods: We analyzed clinical features, treatment, and...

Assessing the feasibility and validity of the Toronto Childhood Cancer Stage Guidelines: a population-based registry study

Cancer stage at diagnosis is crucial for assessing global efforts to increase awareness of childhood cancer and improve outcomes. However, consistent information on childhood cancer stage is absent from population cancer registries worldwide. The Toronto Childhood Cancer Stage Guidelines, compiled through an international consensus process, were designed to provide a standard framework for collection of information on stage at diagnosis of childhood cancers. We aimed to assess the feasibility of implementing the Toronto Guidelines within a national population cancer registry. We did a population-based registry study using data from the Australian Childhood Cancer Registry and included data from children aged 0-14 years diagnosed between Jan 1, 2006, and Dec 31, 2010 with one of 16 childhood cancers listed in the Toronto Guidelines (acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin's lymphoma, non-Hodgkin lymphoma, neuroblastoma, Wilms' tumour, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma, hepatoblastoma, testicular cancer, ovarian cancer, medulloblastoma, and ependymoma). We extracted data from medical records, and assigned stage according to the Tier 1 criteria (basic) and Tier 2 criteria (more detailed, requiring data from cytology, imaging, and other diagnostic tests, where available) using computer algorithms derived from the Toronto Guidelines. Additionally, expert reviewers independently assigned Tier 2 stage to a random subsample of 160 cases (ten per malignancy type). Feasibility of the guidelines was assessed on the percentage of cases that could be staged, agreement between stage assigned by the algorithms and the expert reviewers, and the mean time (min) taken to collect the required data. We obtained data for 1412 eligible children. Stage could be assigned according to Tier 2 criteria for 1318 (93%) cases, ranging from 48 (84%) of 57 cases of non-rhabdomyosarcoma soft tissue sarcoma to 46 (100%) cases of hepatoblastoma. According to Tier 1 criteria, stage could be assigned for 1329 (94%) cases, ranging from 131 (87%) of 151 cases of acute myeloid leukaemia to 46 (100%) cases of hepatoblastoma. By contrast, stage at diagnosis was recorded by the treating physician for 555 (39%) of the 1412 cases. The computer algorithm assigned the same stage as did one or more independent expert reviewers in 155 (97%) of the 160 cases assessed. The mean time taken to review medical records and extract the required data was 18·0 min (SD 9·5 per case). The Toronto Guidelines provide a highly functional framework that can be used to assign cancer stage at diagnosis using data routinely available in medical records for most childhood cancers. Data on staging have the potential to inform interventions targeting improved diagnosis and survival. Cancer Australia.

Extraskeletal osteosarcoma: A large series treated at a single institution.

Purpose: This study is to present a large cohort of extraskeletal osteosarcoma (ESOS) and evaluate prognostic factors and treatment options. Methods: Medical records were reviewed retrospectively for 41 patients with extraskeletal osteosarcoma that was diagnosed by pathology, and treated at our institution between 1960 and 2016. Kaplan-Meier analysis and Cox proportional hazards regression were used to identify variables that affect survival outcomes. Results: 41 patients were identified from 952 osteosarcomas. 32 patients had non-metastatic disease. Prognostic factors were identified by univariate analysis and multi-variate analysis. Surgery (p<0.001), and surgery type (p<0.001) both were shown to significantly affect overall survival (OS). Chemotherapy and radiation therapy (RT) did not show any significant effect on OS, local recurrence, or progression free survival as a whole. However for patients who had incomplete resection with residual tumor RT improved OS (p=0.03). The survival curve for ESOS follows more closely that of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Conclusions: ESOS is a very rare tumor. Attempt to achieve wide resection is the treatment of choice. However for patients who are not able to achieve complete resection, RT may improve OS. The behavior of ESOS more closely follows that of NRSTS than osteosarcoma of the bone.

Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study)

PurposeWe evaluated the role of bevacizumab as part of the multi-modality treatment of children and adolescents with metastatic rhabdomyosarcoma (RMS) or non-rhabdomyosarcoma soft tissue sarcoma (NRSTS). Patients and methodsEligible patients aged ≥6 months to <18 years were randomised to receive induction chemotherapy (four cycles of IVADo + five cycles of IVA, ±bevacizumab), surgery and/or radiotherapy, followed by maintenance chemotherapy (12 cycles of low-dose cyclophosphamide + vinorelbine, ±bevacizumab). The primary objective was event-free survival (EFS) evaluated by an independent radiological review committee. ResultsOne hundred and fifty-four patients were randomised to receive chemotherapy alone (n = 80) or with bevacizumab (n = 74). At the data cut-off for the primary efficacy analysis, median EFS was 14.9 months (95% confidence interval [CI]: 10.8–35.9) with chemotherapy and 20.6 months (95% CI: 15.2–24.9) with bevacizumab plus chemotherapy (stratified hazard ratio [HR] = 0.93; 95% CI: 0.61–1.41; P = 0.72). The HR for EFS in patients with RMS (n = 103) was 1.24 (95% CI: 0.73–2.09) versus 0.64 (95% CI: 0.32–1.26) for those with NRSTS (n = 49). Objective response rate was 36.0% (95% CI: 25.2–47.9) with chemotherapy and 54.0% (95% CI: 40.9–66.6) with bevacizumab plus chemotherapy (difference of 18.0%; 95% CI: 0.6–35.3). There were no treatment-related deaths and no increased incidence of grade 3/4 toxicities with bevacizumab. ConclusionThe addition of bevacizumab to chemotherapy appeared tolerable in children and adolescents with metastatic RMS/NRSTS, but the primary end-point of EFS did not show statistically significant improvement.Trial registration: ClinicalTrials.gov, NCT00643565.

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.