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PubMed2026

Circulating Tumor DNA Profiling Defines Risk Classification in Patients With Ewing Sarcoma: A Report From the Children's Oncology Group and the LEOPARD Study.

PURPOSE: Identification of discrete risk groups remains a high priority for patients with Ewing sarcoma (EWS). We sought to prospectively validate circulating tumor DNA (ctDNA) as a prognostic factor and develop clinical-molecular risk groups. METHODS: We conducted a prospective investigator-initiated biology study for patients with localized EWS (LEOPARD) and embedded ctDNA analysis into the North American frontline metastatic study AEWS1221. Eligible patients were younger than 50 years with newly diagnosed EWS. All patients provided a baseline blood sample for analysis, which was subjected to ultralow-pass whole-genome sequencing and hybrid capture panel sequencing for ctDNA quantification, fusion detection, and characterization of STAG2 and TP53 alterations. Serial ctDNA sequencing was conducted on a subset of patients in each study. We tested for associations between ctDNA burden and secondary genomic events, and clinical features and outcomes. RESULTS: One hundred forty patients with localized disease and 255 with metastatic disease provided evaluable pretreatment samples for ctDNA analysis. Elevated baseline ctDNA was associated with stage, tumor size, primary site, indeterminate pulmonary nodules, and metastatic pattern. Elevated pretreatment ctDNA burden was associated with inferior outcomes in patients with localized (n = 140, hazard ratio [HR] = 2.36, P = .032) and metastatic disease (n = 255, HR = 2.15, P = .001). Patients with metastatic disease and TP53 variants and/or persistent on-therapy ctDNA had dismal outcomes. Patients with localized disease, low ctDNA, small tumors, and favorable genomics had no events and constitute a novel low-risk group. Among patients with metastatic disease, those with lung-only disease, low ctDNA, and favorable genomics represent an intermediate-risk group. CONCLUSION: This study prospectively validates pretreatment ctDNA burden as prognostic in EWS. Risk groups that integrate ctDNA burden with clinical-molecular features differentiate patients with low-, intermediate-, and high-risk disease.

Journal Article↗

PubMed1979

Osteogenic sarcoma: the past, present, and future.

The term osteogenic sarcoma (osteosarcoma) is applied to malignant bone-forming tumors, identifiable by the matrix produced, though the histologic pattern may differ greatly. Ths more cellular (osteolytic) forms of the tumor have the poorer prognosis. Other prognostic factors are 1) site of the primary tumor; 2) duration of symptoms; and 3) extent of disease and tumor size. The site of tumor origin is the metaphyseal side of the epiphyseal line. The histogenesis of the tumors accounts for this distribution. Following a diagnostic biopsy, amputation of the extremities remains the treatment of choice. In selected cases, a limb-saving radical en bloc resection may surface. Radiotherapy plays a lesser but important role as adjunctive treatment, and as primary definitive treatment in certain types of bone sarcoma (Ewing sarcoma and primary reticulum cell sarcoma of bone). Until recently, chemotherapeutic agents have been used for late palliation only. Advances in treatment, however, have resulted from the application of innovative postsurgical adjuvant chemotherapy in children. The various chemotherapeutic regimens following amputation in adults and in children are discussed. In most such series of cases following amputation alone, five-year survivals have not exceeded 15-20%, with recurrent disease appearing within 18 months in fatal cases. Current studies reflect more effective regimens of adjuvant chemotherapy, with improved palliative results in metastatic osteogenic sarcoma. Although survival is much prolonged, however, many patients show a recurrence of the disease after long intervals of control, suggesting that five-year survival may not indicate a complete cure. At M.D. Anderson Hospital, th projected overall survival rate at three years is 79% of all patients with nonmetastatic disease. These results have accrued from the use of Compadri-I and Compadri-II regimens of chemotherapy. More intensive therapy may yield higher survival rates. It is known that the immunologic status of a patient definitely relates to prognosis. Although most of the investigations with immunotherapy are preliminary, emphasis is placed on improving the immune system in immunodeficient patients.

Adolescent↗

PubMed1978

[Contribution to central nervous system tumor diagnosis by means of cytocentrifuged cerebrospinal fluid].

The cytocentrifugation of the liquor cerebrospinalis provides a useful diagnostic tool to differentiate benign from malign diseases of the central nervous system. The method is illustrated with liquor analyses in the field of pediatric oncology: medulloblastoma, leptomeninx sarcoma, plexuspapilloma, astrocytoma, Abt-Letterer-Siwe, ALL, reticulum cell sarcoma, Ewing sarcoma, retinoblastoma. The speed and ease of the processing, the highest possible cellular yield and the good preservation of the cellular characteristics are great advantages of this new method.

Brain Neoplasms↗

PubMed1977

Leukocyte migration inhibition in patients with Ewing's sarcoma by 3-M potassium chloride extracts of fresh and tissue-cultured Ewing's sarcomas.

Leukocyte migration inhibition (LMI) assays were performed to detect cell-mediated immune reactions against tumor-associated antigens (TAA) of Ewing's sarcoma. With the use of crude antigen preparations obtained by 3M KCl extractions of fresh Ewing's sarcoma or of tissue culture cells derived from a pleural effusion of a Ewing's sarcoma patient, assays were performed with leukocytes from these patients, patients with other cancers, and normal donors. The results demonstrated approximately 60% or greater positive LMI reactivity in Ewing's sarcoma patients, as compared to less than 10% reactivity of normal donors, with the use of extracts of either fresh or tissue-cultured Ewing's sarcoma cells. A lower proportion of positive reactivity was observed in patients with breast and lung cancer. Further specificity tests indicated that a smaller proportion of patients with Ewing's sarcoma had LMI reactivity with KCl extracts of tissue-cultured cells derived from breast cancer of fresh lung cancer cells than did patients with the homologous disease. The results indicate that many patients with Ewing's sarcoma have cell-mediated immunity toward TAA on Ewing's sarcomas. Inasmuch as all the LMI assay were performed with allogeneic extracts, the data also suggested that different Ewing's sarcomas possess common antigens and that some breast and lung cancers may share some TAA with Ewing's sarcoma.

Antigens, Neoplasm↗

PubMed1977

Ewing's sarcoma of the mandible.

Ewing's sarcoma of the head and neck, particularly of the mandible, has a low incidence of occurrence (fifty-five cases in the literature). The present case report demonstrates well the clinical, diagnostic, and therapeutic features in a patient treated at the Head and Neck Service of the Fundação Antonio Prudente, São Paulo, Brazil. The etiologic, clinical, histopathologic, and radiologic features are discussed, with the conclusion that radiation is the best therapeutic procedure when associated with chemotherapy.

Adult↗

PubMedDate not supplied

Ewing's sarcoma of the mandible.

Ewing's sarcoma of the mandible occurs rarely; there have been less than 50 reported cases in the past 30 years and none of these have been in the otolaryngologic literature. They usually present in the second decade of life with pain and swelling of the soft tissue overlying the mandible. The diagnosis can only be made by an adequate mandibular biopsy, although x-rays and clinical presentation are helpful. Current treatment consists of radiation therapy and sequential adjuvant chemotherapy.

Adolescent↗

PubMed1976

Prophylactic irradiation of the lung in Ewing's sarcoma.

A patient with Ewing's sarcoma of the left scapula received prophylactic radiotherapy to the left lung following wide excision of the tumor. While the left lung remained free of tumor, there was metastatic invasion of the right lung within ten months of the initial diagnosis of the disease. Since Ewing's sarcoma frequently metastasizes to the lungs, it is suggested that prophylactic irradiation of the lung may be of value in the prevention of metastases.

Adult↗

PubMed1979

Primary epidural Ewing's sarcoma presenting as a lumbar disc protrusion. Case report.

Primary neoplasms of the spinal epidural space are uncommon. One of the rarest of these is a soft tissue sarcoma indistinguishable from Ewing's sarcoma of the bone. Only 39 such cases have been reported previously, of which only three arose within the epidural space. The authors report an additional case, which presented in an atypical manner, and review the pertinent literature.

Adult↗

PubMed1977