Neighborhood Socioeconomic Status and Overall Survival among Children with Acute Lymphoblastic Leukemia.

A disadvantaged neighborhood, as represented by area-level socioeconomic status (SES) has been associated with adverse outcomes among children with acute lymphoblastic leukemia (ALL) in the US, but the duration of impact after ALL diagnosis is not well understood. This retrospective cohort study utilized the National Cancer Database (NCDB) to examine the impact of area-level SES on overall survival among children with ALL. Median income and education quartiles based on residential zip code were used to create a composite area-level SES variable.

A Phase 1 Study of ABI-009 (Nab-sirolimus) in Combination With Temozolomide and Irinotecan in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study ADVL1514.

Background: Nab-sirolimus (ABI-009, nab-rapamycin; Aadi Bioscience Inc. [Aadi]) is a human albumin-bound form of sirolimus nanoparticles, a potent mTOR inhibitor. This phase I trial was conducted to define dose-limiting toxicities (DLT), maximum tolerated or recommended phase II dose (MTD/RP2D), and pharmacokinetics of Nab-sirolimus in combination with temozolomide and irinotecan.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

Strategies for the Treatment of Infantile Soft Tissue Sarcomas With BCOR Alterations.

BCOR alterations are described in ultra-rare infantile soft tissue sarcomas including primitive myxoid mesenchymal tumor of infancy and undifferentiated round cell sarcoma (URCS). Previous reports often describe dismal outcomes. Thus, we undertook a retrospective, multi-institutional study of infants with BCOR -rearranged soft tissue sarcomas.

Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers.

RAF family protein kinases signal through the MAPK pathway to orchestrate cellular proliferation, survival, and transformation. Identifying BRAF alterations in pediatric cancers is critically important as therapeutic agents targeting BRAF or MEK may be incorporated into the clinical management of these patients. In this study, we performed comprehensive genomic profiling on 3,633 pediatric cancer samples and identified a cohort of 221 (6.

Integrating genetic counseling and testing in the pediatric oncology setting: Parental attitudes and influencing factors.

Background: Cancer predisposition syndromes (CPS) are caused by germline pathogenic variants that put an individual at increased risk of developing cancer throughout their lifetime. It is estimated that approximately 10-15% of children with cancer have an underlying CPS. Although research has investigated the clinical utility of genetic testing for children diagnosed with cancer, this study aimed to gain a deeper understanding of parental attitudes toward genetic testing in this population.

Clinicopathologic Features of a Series of Primary Renal CIC-rearranged Sarcomas With Comprehensive Molecular Analysis.

CIC-rearranged sarcomas rarely occur in visceral organs including the kidney. The most common fusion partner with CIC is the DUX4 gene, but variant fusion partners have also been reported. Herein, we describe the clinicopathologic features and comprehensive molecular profiling of 4 cases of primary renal CIC-rearranged sarcomas.

Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study.

Therapy for rhabdomyosarcoma (RMS) has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types.

Whole exome sequencing identified sixty-five coding mutations in four neuroblastoma tumors.

Neuroblastoma is a pediatric tumor characterized by histologic heterogeneity, and accounts for ~15% of childhood deaths from cancer. The five-year survival for patients with high-risk stage 4 disease has not improved in two decades. We used whole exome sequencing (WES) to identify mutations present in three independent high-risk stage 4 neuroblastoma tumors (COA/UAB-3, COA/UAB -6 and COA/UAB -8) and a stage 3 tumor (COA/UAB-14).

Successful Treatment of Recurrent Primitive Myxoid Mesenchymal Tumor of Infancy With Internal Tandem Duplication.

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare tumor with <20 cases reported to date. Recently PMMTI tumors have been found to harbor internal tandem duplication (ITD), the same genetic alteration detected in clear cell sarcoma of the kidney (CCSK). Complete surgical resection of PMMTI is often curative, but no standard of care has been established for unresectable tumors.

Gorham-Stout Disease Successfully Treated With Sirolimus and Zoledronic Acid Therapy.

Gorham-Stout disease is a life-threatening disorder often manifested by lymphatic malformation and osteolysis. Unfortunately, available therapies are not uniformly effective and often carry substantial morbidity. We report an 18-year-old male with Gorham-Stout disease manifested by lytic rib lesions and an intractable pleural effusion that responded dramatically to the combination of the mammalian target of rapamycin (mTOR) inhibitor sirolimus and the aminobisphosphonate zoledronic acid after failing interferon therapy.

Transition from open to robotic-assisted radical prostatectomy is associated with a reduction of positive surgical margins amongst private-practice-based urologists.

Several recent studies have suggested that thought leaders in radical prostatectomy have decreased their own positive margin rates by switching from open to robot-assisted radical prostatectomy. Theoretically, this improvement is largely attributed to enhanced visualization of the deep pelvis and precision of dissection afforded by the instrumentation. To date, it has not been determined if this phenomenon exists amongst non-fellowship-trained urologists in private practice.

Physiological importance of system A-mediated amino acid transport to rat fetal development.

Fetal growth and development are dependent on the delivery of amino acids from maternal amino acid pools to the fetal blood. This is accomplished via transfer across the apical and basal plasma membrane of the placental syncytiotrophoblast. The aim of this study was to determine whether inhibition of system A (amino acid transporter) was associated with a decrease in fetal weight in the rat.