Molecular characterization informs prognosis in patients with localized Ewing sarcoma: A report from the Children's Oncology Group.

Purpose: Identification of discrete sub-groups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children's Oncology Group biology study AEWS18B1-Q was to perform molecular characterization of a large cohort of patients with localized Ewing sarcoma treated on prospective trials with modern standard of care therapy.

Methods: We analyzed clinical and molecular features from patients with localized EWS enrolled on AEWS0031, AEWS1031, or INT-0154 frontline trials.

Rhabdomyosarcoma With EWSR1::NF2 Gene Fusion: A Case Report Potentially Expanding Its Genetic Spectrum.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, presenting with heterogeneous clinical and molecular subtypes. While gene fusions are predominantly associated with alveolar RMS, spindle cell RMS, especially congenital and intraosseous variants, are also linked to specific gene fusions. Furthermore, recently, FGFR1 kinase-driven RMSs were published.

Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations.

"It Was a Downward Spiral": A Qualitative Study of Young Adult Cancer Survivors' Experiences with Cognitive and Mental Health.

Cancer-related cognitive impairment (CRCI) is common and distressing for young adult (YA) cancer survivors; however, subjective CRCI is often attributed to psychological distress rather than true cognitive change. Thus, we aimed to generate hypotheses regarding potential common biobehavioral mechanisms of CRCI and psychological distress. We conducted semi-structured interviews with YA cancer survivors in peak years for frontal neurocognitive development (ages 18-30), and we asked them to describe their experiences with cognitive and mental health changes during and after treatment for their cancer.

Hypofractionated accelerated radiation dose-painting (HARD) improves outcomes in unresected soft-tissue sarcoma.

Soft tissue sarcomas (STS) are radioresistant with a low α/β, which may have a biologic benefit with hypofractionation. For unresectable STS, the dose escalation required to achieve durable control is often limited by long-term toxicity risk. We sought to compare an isotoxic approach utilizing hypofractionated accelerated radiation dose-painting (HARD) versus standard fractionated radiation therapy (SFT) in patients with unresected STS.

Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.

The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS.

Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function.

The human CMG helicase (Cdc45-MCM-GINS) is a novel target for anticancer therapy. Tumor-specific weaknesses in the CMG are caused by oncogene-driven changes that adversely affect CMG function, and CMG activity is required for recovery from replicative stresses such as chemotherapy. Herein, we developed an orthogonal biochemical screening approach and identified CMG inhibitors (CMGi) that inhibit ATPase and helicase activities in an ATP-competitive manner at low micromolar concentrations.

Poverty, race, ethnicity, and survival in pediatric nonmetastatic osteosarcoma: a Children's Oncology Group report.

Background: Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial.

Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience.

Objectives: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients.

Materials And Methods: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed.

Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

"I couldn't connect the wires in my brain." Young adult cancer survivors' experience with cognitive functioning.

Objective: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors.

Methods: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.

Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031.

JCO Long-term outcomes from Children's Oncology Group study AEWS0031 were assessed to determine whether the survival advantage of interval-compressed chemotherapy (ICC) was maintained over 10 years in patients with localized Ewing sarcoma (ES). AEWS0031 enrolled 568 eligible patients. Patients were randomly assigned to receive vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide alternating once every 3 weeks (standard timing chemotherapy [STC]) versus once every 2 weeks (ICC).

Identification of Selective ATP-Competitive CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function.

The human CMG helicase (Cdc45-MCM-GINS) is a novel target for anti-cancer therapy due to tumor-specific weaknesses in CMG function induced by oncogenic changes and the need for CMG function during recovery from replicative stresses such as chemotherapy. Here, we developed an orthogonal biochemical screening approach and identified selective CMG inhibitors (CMGi) that inhibit ATPase and helicase activities in an ATP-competitive manner at low micromolar concentrations. Structure-activity information and docking indicate that CMGi occupy ATP binding sites and channels within MCM subunits leading to the ATP clefts, which are likely used for ATP/ADP ingress or egress.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

The Lived Experience of Young Adult Cancer Survivors after Treatment: A Qualitative Study.

Objective: The purpose of this qualitative study was to compare the lived experiences among extended (one year or less post-treatment) and long-term (three years or more post-treatment) young adult (YA) cancer survivors (ages 18-39 years old).

Methods: Two trained researchers conducted semi-structured interviews inquiring about the overall lived experience of = 24 YA cancer survivors ( = 12 extended and = 12 long-term). The same two researchers independently completed line-by-line coding and thematic content analysis.

Children's Oncology Group's 2023 blueprint for research: Bone tumors.

The Children's Oncology Group (COG) Bone Tumor Committee is responsible for clinical trials and biological research on localized, metastatic, and recurrent osteosarcoma and Ewing sarcoma (EWS). Results of clinical trials in localized disease completed and published in the past 10 years have led to international standard-of-care chemotherapy for osteosarcoma and EWS. A recent focus on identifying disease subgroups has led to the identification of biological features associated with poor outcomes including the presence of circulating tumor DNA (ctDNA) at diagnosis, and specific genomic alterations-MYC amplification for osteosarcoma and STAG2 and TP53 mutation for EWS.

Social isolation and social connectedness among young adult cancer survivors: A systematic review.

Background: Social isolation and connectedness are social determinants of health that have demonstrated effects on cancer-related outcomes. These constructs have been systematically evaluated among pediatric and older adult cancer populations. In this review, the authors evaluated the prevalence, correlates, and psychosocial implications of social isolation and connectedness among young adult (YA) cancer survivors aged 18-39 years.

Children's Oncology Group 2023 blueprint for research: Adolescent and young adult oncology.

Over the past few decades, 5-year cancer survival has steadily improved for all adolescents and young adults (AYA, 15-39 years at diagnosis) combined. While encouraging, this progress simultaneously highlights a compelling need for improving survival in higher risk AYA subsets and for addressing health outcomes and health-related quality of life (HRQoL) among long-term survivors. The Children's Oncology Group (COG), in collaboration with the National Cancer Institute (NCI) and the adult network groups within the NCI National Clinical Trials Network (NCTN), has developed a large and growing portfolio of therapeutic AYA cancer clinical trials to identify optimal treatment approaches for common AYA cancers.

Bad to the Bone: Emerging Approaches to Aggressive Bone Sarcomas.

Bone sarcomas are rare heterogeneous tumors that affect patients of all ages including children, adolescent young adults, and older adults. They include many aggressive subtypes and patient groups with poor outcomes, poor access to clinical trials, and lack of defined standard therapeutic strategies. Conventional chondrosarcoma remains a surgical disease, with no defined role for cytotoxic therapy and no approved targeted systemic therapies.

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype?

Background: Immune checkpoint inhibitors (ICIs) have shown modest antitumor activity in unselected advanced sarcomas. Histology driven approach to patient selection is the current standard for off-label anti-programmed cell death 1 (PD1) immunotherapy use.

Methods: We retrospectively reviewed the clinical characteristics and outcomes of patients with advanced sarcoma who were treated with off label anti-PD1 immunotherapy at our center.

Trends in Overall Survival among Patients Treated for Sarcoma at a Large Tertiary Cancer Center between 1986 and 2014.

Sarcomas are relatively rare malignancies accounting for about 1% of all cancer diagnoses. Studies on sarcomas comprising large cohorts covering extended time periods are lacking. Therefore, this study aimed to evaluate the impact of demographic, behavioral, and clinical characteristics on overall survival (OS) among individuals diagnosed with soft tissue sarcoma (STS) or bone sarcoma at the Moffitt Cancer Center between 1986 and 2014.

Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group.

Purpose: Monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) have shown activity in patients with relapsed Ewing sarcoma. The primary objective of Children's Oncology Group trial AEWS1221 was to determine if the addition of the IGF-1R monoclonal antibody ganitumab to interval-compressed chemotherapy improves event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma.

Methods: Patients were randomly assigned 1:1 at enrollment to standard arm (interval-compressed vincristine/doxorubicin/cyclophosphamide alternating once every 2 weeks with ifosfamide/etoposide = VDC/IE) or to experimental arm (VDC/IE with ganitumab at cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy).