Publications by authors named "London W"
Purpose: Novel therapies targeting specific genomic alterations are a promising treatment approach for relapsed/refractory cancer. Patients with specific alterations may be more likely to respond. Trial designs should maximize opportunities for such patients to enroll on these trials.
View Article and Find Full Text PDFPurpose: The fragility index (FI) is an adjunctive metric to facilitate the interpretation of p-values in clinical trials. The FI has not been studied in phase 3 trials in pediatric oncology.
Methods: PubMed was used to identify phase 3 pediatric oncology trials published between 1980 and 2020.
Article Synopsis
- Tumor invasion of the spinal canal occurs in about 15% of newly diagnosed neuroblastoma patients, prompting a need for effective treatment strategies that optimize survival while minimizing long-term effects.
- A study of 92 intermediate-risk neuroblastoma patients with intraspinal tumors revealed that nearly half were symptomatic at diagnosis, but most of them experienced complete resolution of symptoms following treatment, regardless of the initial severity or duration of their deficits.
- The findings suggest that while prompt diagnosis and chemotherapy are crucial, surgical options like laminectomy may not significantly improve motor symptoms, indicating that surgery should be reserved for cases with rapid worsening neurologic conditions.
Article Synopsis
- The study analyzed trends in the diagnosis of venous thromboembolism (VTE) and arterial ischemic stroke (AIS) in pediatric patients during the COVID-19 pandemic, using data from the Pediatric Health Information Systems database from 2018 to 2021.
- The rate of VTE diagnoses increased by 28.6% during the pandemic years compared to previous years, while AIS rates remained stable; COVID-19 diagnosis was linked to a higher likelihood of VTE but not AIS.
- Utilization of pharmacological thromboprophylaxis doubled during the pandemic, especially among patients with COVID-19, indicating a significant response in treatment approaches despite the rising rates of VTE.
Background: The International Neuroblastoma Risk Group (INRG) classifier utilizes a staging system based on pretreatment imaging criteria in which image-defined risk factors (IDRFs) are used to evaluate the extent of locoregional disease. Children's Oncology Group (COG) study ANBL0531 prospectively examined institutional determination of IDRF status and compared that to a standardized central review.
Methods: Between 9/2009-6/2011, patients with intermediate-risk neuroblastoma were enrolled on ANBL0531 and had IDRF assessment at treating institutions.
Background: The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes.
Methods: Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019.
Article Synopsis
- A study conducted at Dana-Farber/Boston Children's Cancer and Blood Disorders Center focused on classifying pediatric solid tumor diagnoses and analyzing genomic mutations to improve clinical trial design and treatment options.
- Over 6.5 years, the research included 888 pediatric cancer patients, revealing that 33% had genomic variants that aligned with precision oncology trials, while 14% received targeted therapies.
- The findings stress the significance of using genomic data for enhancing treatment strategies and the necessity for data sharing, particularly for addressing rare pediatric cancers in clinical settings.
Background: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results.
Methods: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible.
The health care use (HCU) burden of transplant-associated thrombotic microangiopathy (TA-TMA) and its treatments are unknown. The objective of this study was to investigate inpatient costs associated with meeting criteria for TA-TMA in the first year after hematopoietic cell transplant (HCT). This institutional review board-approved retrospective multicenter study included serial children who underwent HCT from 1 January 2015 to 1 July 2019.
View Article and Find Full Text PDFBackground: Pediatric melanoma presents with distinct clinical features compared to adult disease.
Objective: Characterize risk factors and negative outcomes in pediatric melanoma.
Methods: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers.
Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention.
View Article and Find Full Text PDFPurpose: Phase 1 study assessing the safety and toxicity of cabozantinib in combination with topotecan and cyclophosphamide for relapsed osteosarcoma and Ewing sarcoma.
Methods: Oral cabozantinib (25 mg/m ) was administered daily for 21 (dose level 1) or 14 (dose level -1B) days. Topotecan (0.
Purpose: Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB.
Patients And Methods: Tumors were molecularly screened to confirm the diagnosis of WNT+MB.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.
View Article and Find Full Text PDFBackground And Purpose: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images.
Materials And Methods: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed.
Background: Ewing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin-dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF-1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF-1R monoclonal antibody) for patients with relapsed EWS.
View Article and Find Full Text PDFBackground: Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available.
Methods: We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure.
Background: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end-of-induction (EOI) Curie scores (CS) was previously described in patients undergoing a single course of high-dose chemotherapy (HDC) and autologous hematopoietic cell transplant (AHCT) as consolidation therapy.
Objective: We now examine the prognostic significance of CS in patients randomized to tandem HDC and AHCT on the Children's Oncology Group (COG) trial ANBL0532.
Purpose: In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.
Patients And Methods: Children <3 years old at diagnosis, enrolled on a COG biology study from 1990 to 2018, were eligible (n = 9,189).
Background: In the Children's Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined with either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) and granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among patients treated with I/T/DIN/GM-CSF in the initial cohort (n=17) was 53%; additional patients were enrolled to permit further evaluation of this chemoimmunotherapy regimen. Potential associations between immune-related biomarkers and clinical outcomes including response and survival were evaluated.
View Article and Find Full Text PDFPurpose: To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease.
Methods: Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms.
Background: Outcomes for patients with INRGSS metastatic special (MS) metastatic pattern neuroblastoma at initial diagnosis are well described. Prognosis after an initial event (relapse, progression, secondary malignancy) is unclear.
Methods: We investigated characteristics of MS pattern neuroblastoma patients in the International Neuroblastoma Risk Group database who subsequently experienced an event.