Publications by authors named "Campbell-Hewson Q"
We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.
View Article and Find Full Text PDFImportance: In poor-prognosis children's cancers, new therapies may carry fresh hope for patients and parents. However, there is an absolute requirement for any new therapy to be properly evaluated to fulfill scientific, regulatory, and reimbursement requirements. Randomized clinical trials (RCTs) are considered the gold standard, but no consensus exists on how and when they should be deployed to best meet the needs of all stakeholders.
View Article and Find Full Text PDFImportance: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.
Objective: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.
Design, Setting, And Participants: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America.
Article Synopsis
- Osteosarcoma and Ewing sarcoma are challenging bone tumors primarily affecting younger individuals, with low survival rates even after various treatment approaches.
- Current research on targeted therapies and immunotherapies has been ineffective, highlighting the need for a deeper understanding of the tumor biology and the immune microenvironment.
- A new Europe-wide framework for systematic sampling and analysis of patient samples has been proposed, supported by international consortia aiming to set guidelines that will enhance research collaboration and ultimately improve treatment outcomes.
Article Synopsis
- A phase Ib study investigated the safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of regorafenib when combined with vincristine and irinotecan for treating kids with relapsed/refractory solid tumors, primarily rhabdomyosarcoma.
- The study involved 21 patients, determining the MTD/RP2D of regorafenib at 82 mg/m2 when given sequentially; adverse effects mostly included severe blood-related issues, with varying levels of response observed in tumors.
- Findings suggest that regorafenib can be safely combined with vincristine and irinotecan in pediatric settings, showing promising clinical activity for certain types of tumors.
The eighth Paediatric Strategy Forum focused on multi-targeted kinase inhibitors (mTKIs) in osteosarcoma and Ewing sarcoma. The development of curative, innovative products in these tumours is a high priority and addresses unmet needs in children, adolescents and adults. Despite clinical and investigational use of mTKIs, efficacy in patients with bone tumours has not been definitively demonstrated.
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- The MAPK pathway is being targeted in various tumors, and MEK1 inhibitors like cobimetinib are proposed to manage MAPK-dependent cancers in young patients.
- The iMATRIX-cobi study evaluated the safety and anti-tumor effects of cobimetinib in children and young adults aged 6 months to 30 years with solid tumors linked to the MAPK pathway.
- The results showed that while the safety profile for cobimetinib was similar to adults, only a few patients (5.4%) experienced partial tumor responses, indicating the need for further combination treatments to enhance effectiveness.
Article Synopsis
- SARS-CoV-2 infections in children are mostly mild, even in those with weakened immune systems.
- A small percentage may experience severe symptoms, necessitating intensive care.
- This report details a teenager with Hodgkin's lymphoma who developed serious respiratory issues after getting SARS-CoV-2 during her stem cell transplant, but was successfully treated with antivirals, steroids, and ECMO.
Article Synopsis
- Therapeutic Drug Monitoring (TDM) is underused in childhood cancer treatment, even though cytotoxic chemotherapies are common, due to variability in drug effectiveness and toxicity among patients.
- *Recent advances in TDM have encouraged its adoption in pediatric oncology, especially for vulnerable groups like infants and patients with kidney issues, allowing for more personalized dosing strategies.
- *The article reviews experiences and perspectives on TDM implementation in childhood cancer care, highlighting its potential to optimize dosing and improve outcomes among challenging patient populations.
Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274).
Patients And Methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D.
Article Synopsis
- This study investigates the effectiveness of a treatment combining lenvatinib, etoposide, and ifosfamide in young patients with relapsed or refractory osteosarcoma, aiming to find the optimal dosage and assess its anti-tumor activity.
- Conducted in 17 hospitals across six countries, the trial focused on patients aged 2-25 with measurable disease and a life expectancy of at least 3 months, evaluating safety and progression-free survival.
- Thirty patients were screened for the initial phase, with 22 participants advancing to the second phase, assessing how well the combination therapy works over a maximum of five treatment cycles followed by lenvatinib alone.
Article Synopsis
- Kes survival rates for relapsed/refractory osteosarcoma are low, but kinase inhibitors like lenvatinib have shown promise in treatment.
- A Phase II study revealed that the combination of lenvatinib with ifosfamide and etoposide exhibited anti-tumor activity in affected patients.
- The ongoing OLIE trial aims to compare the effectiveness of this combination treatment against ifosfamide and etoposide alone in young patients, with key goals focusing on progression-free survival and other safety and quality of life measures.
Article Synopsis
- * A case study highlights a 7-month-old infant with an incidental pelvic NBL located at the dome of the urinary bladder, classified as very low risk and treated successfully with surgical excision.
- * After 5 years of follow-up, the infant remained disease-free, suggesting that NBL should be part of the differential diagnosis for urinary bladder masses in children.
Article Synopsis
- Alveolar soft-part sarcoma (ASPS) is a rare and treatment-resistant cancer, with the CASPS study aiming to evaluate the effectiveness of the tyrosine-kinase inhibitor cediranib against this disease, distinguishing its effects from the cancer's natural slow progression.
- The study was a double-blind, placebo-controlled trial conducted across 12 hospitals in the UK, Spain, and Australia, involving patients aged 16 and older with advanced ASPS who had not received recent cancer treatment.
- Participants were randomly assigned to receive either cediranib or a placebo for 24 weeks, with the main outcome measured being the change in tumor marker sizes, while safety was monitored throughout the trial.
Article Synopsis
- A phase I trial of AT9283, a drug targeting Aurora kinases A and B, was conducted with children and adolescents who have solid tumors to assess its safety, efficacy, and maximum-tolerated dose (MTD).
- The drug was given through a continuous intravenous infusion for 72 hours every three weeks, with six different dose levels explored; the MTD was determined to be 18.5 mg/m²/day.
- While the treatment had manageable side effects mainly involving blood-related issues, it showed effectiveness with some patients achieving stable disease, and target inhibition was confirmed through biomarker analysis.
Article Synopsis
- A child was diagnosed with Wilm's tumor that had spread into the inferior vena cava and extended to the right ventricle of the heart.
- The rapid growth of the tumor-thrombus caused severe health complications, which were identified through imaging techniques.
- After emergency chemotherapy, the child's condition improved quickly, allowing for successful surgical removal of the tumor, and she is now in remission.