Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab.

Purpose: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.

Methods: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono).

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab.

What Is This Summary About?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.

What Were The Results?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects.

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer.

Purpose: Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer.

Purpose: Cisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many patients with la/mUC are ineligible. Each enfortumab vedotin and pembrolizumab have shown a survival benefit versus chemotherapy in UC, are not restricted by cisplatin eligibility, and warrant investigation as a first-line (1L) combination therapy in patients ineligible for cisplatin.

Methods: In this ongoing phase Ib/II, multicenter, open-label study, 1L cisplatin-ineligible patients with la/mUC received enfortumab vedotin 1.

Langerhans Cell Histiocytosis With Vertebral Involvement Diagnosed and Treated Over the Last 15 Years in a Single Canadian Pediatric Academic Institution.

We report 11 children with vertebral lesion of Langerhans cell histiocytosis (LCH) diagnosed and treated between 2000 and 2015. Vertebral lesions were usually present at LCH diagnosis. No child developed neurologic symptoms.

A phase 1 trial of SGN-CD70A in patients with CD70-positive, metastatic renal cell carcinoma.

Background: Cluster of differentiation 70 (CD70) is frequently expressed in renal cell carcinoma (RCC) and has immunomodulatory properties. An antibody-drug conjugate targeting CD70, SGN-CD70A, was developed to treat patients with CD70-positive RCC.

Methods: The objective of this phase 1, open-label, dose-escalation, multicenter study was to evaluate the safety and tolerability of SGN-CD70A and establish its maximum tolerated dose in patients with CD70-positive, metastatic RCC (mRCC).

A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma.

Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg. Due to observations of prolonged thrombocytopenia, the study was amended to dose every 6 weeks (q6wk).

Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries.

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510).

Most children with cancer are not enrolled on a clinical trial in Canada: a population-based study.

Background: Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials.

Methods: In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012.

Atypical teratoid rhabdoid tumor in the first year of life: the Canadian ATRT registry experience and review of the literature.

While 2/3 of patients with ATRT are less than 3 years at diagnosis, the literature suggests younger children present with more aggressive disease and poorer outcome. However, little data exist on characteristics and outcome of patients diagnosed with ATRT in the first year of life. In particular, it is unclear whether they access similar treatments as do older children.

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors.

Two Cases of Retinoblastoma Invading the Optic Nerve Sheath.

The authors report two cases of retinoblastoma with extension along the optic nerve sheath with negative surgical margins, a pattern not considered in current classifications but suggesting a high risk of metastasis. Both patients were treated with adjuvant chemotherapy alone and remain free of extraocular disease 15 and 22 months later. [J Pediatr Ophthalmol Strabismus.

Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study.

Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible.

Stability and Repeatability of the Distress Thermometer (DT) and the Edmonton Symptom Assessment System-Revised (ESAS-r) with Parents of Childhood Cancer Survivors.

Objective: Parents report psychological distress in association with their child's cancer. Reliable tools are needed to screen parental distress over the cancer trajectory. This study aimed to estimate the stability and repeatability of the Distress Thermometer (DT) and the Depression and Anxiety items of the Edmonton Symptom Assessment System-revised (ESAS-r-D; -A) in parents of children diagnosed with cancer.

Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series.

Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH.

Activities of Daily Living in Survivors of Childhood Brain Tumor.

Objective: This cross-sectional, descriptive study evaluated the performance in activities of daily living (ADLs) of youth and young adult survivors of childhood brain tumor (BT) and explored associations with health-related quality of life (HRQoL).

Method: Thirty-six participants were examined using the Assessment of Motor and Process Skills to evaluate their quality of ADL task performance and the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) to evaluate HRQoL.

Results: Participants had significantly lower performance in ADLs compared with age norms (p < .

SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells.

Retinoblastoma (Rb) is an aggressive childhood cancer of the developing retina. This disease is associated with epigenetic deregulation of several cancer pathways including upregulation of the proto-oncogene spleen tyrosine kinase (SYK). We have previously demonstrated that lymphocyte-derived microparticles (LMPs) possess strong cytotoxic effect on cancer cells.

Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study.

Background: Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients.

Methods: Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions.

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT).

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin.

Survival of children with medulloblastoma in Canada diagnosed between 1990 and 2009 inclusive.

The treatment of medulloblastoma, the most common malignant brain tumor in children, has evolved over the last few decades. The objectives of this paper were to determine the survival of pediatric medulloblastoma in Canada, to determine if there has been an improvement in the survival rates between the years of 1990 and 2009, inclusive, and to determine prognostic factors for survival. All patients under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009, inclusive, in Canada were included.