The Scottish Retinal Detachment Study: 10-year outcomes after retinal detachment repair.

Objective: To address the paucity of long-term data on outcomes following rhegmatogenous retinal detachment (RRD) repair we aimed to establish the 10-year best corrected visual acuity (BCVA), redetachment rate and lens status for patients from the Scottish Retinal Detachment Study.

Subjects: Data from patients who presented with RRD during the original study were collected from clinical records 10 years after repair. Patients were excluded if lacking 10 year follow-up data, and excluded from visual acuity analysis in the case of significant co-morbid ophthalmic disease.

Genomic sequencing in paediatric oncology: navigating conflicting roles and responsibilities.

Background: This study explores the ethical and moral challenges faced by paediatric oncologists when they are informed of patient genomic results, particularly during molecular tumour boards (MTBs), highlighting the interplay between their clinic, research and expert roles.

Methods: This was an explanatory sequential mixed-methods study using a survey distributed to paediatric oncologists in Quebec followed by optional semi-structured interviews. Oncologists' attitudes and comfort levels with six hypothetical germline DNA results identified in a patient from a clinical vignette were assessed using Likert scales.

Clustering of variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a heterogeneous predisposition to an individually variable spectrum of cancers caused by pathogenic germline variants. We used a clustering method to assign TP53 missense variants to classes based on their functional activities in experimental assays assessing biological p53 functions. Correlations with LFS phenotypes were analyzed using the public germline mutation database and validated in three LFS clinical cohorts.

Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance.

Rhabdoid tumor predisposition syndrome type-1 (RTPS1) is characterized by germline pathogenic variants in SMARCB1 and development of INI1-deficient rhabdoid tumors in early childhood. Due to its poor prognosis, the risk of subsequent tumor development and the impact of surveillance at later ages are poorly understood. We retrospectively reviewed individuals referred to the Cancer Genetics Program at The Hospital for Sick Children for SMARCB1 genetic testing and/or surveillance for RTPS1.

Cost-effectiveness of the McGill interactive pediatric oncogenetic guidelines in identifying Li-Fraumeni syndrome in female patients with osteosarcoma.

Background: Li-Fraumeni syndrome (LFS) is a penetrant cancer predisposition syndrome (CPS) associated with the development of many tumor types in young people including osteosarcoma and breast cancer (BC). The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) decision-support tool provides a standardized approach to identify patients at risk of CPSs.

Methods: We conducted a cost-utility analysis, from the healthcare payer perspective, to compare MIPOGG-guided, physician-guided, and universal genetic testing strategies to detect LFS in female patients diagnosed at an age of less than 18 years with osteosarcoma.

Title - Long term outcomes of vitrectomy and ERM peel: Can pre-operative metamorphopsia measured using the D-Chart help improve surgical candidate selection?

Purpose: To assess the predictive value of pre-operative metamorphopsia, measured using the D-Chart, in patients undergoing epiretinal membrane (ERM) surgery and how this relates to improvement in quality of life after surgery.

Methods: 17 patients from vitreo-retinal surgery clinics at a tertiary ophthalmology centre were recruited when listed for pars plana vitrectomy (PPV) with ERM peel between September 2019 - February 2020. Pre-operatively patients underwent visual acuity (VA), Visual-Function Index 14 (VF-14) and metamorphopsia (D-Chart-Thomson Software Solutions) assessment and answered a questionnaire regarding cardinal ERM symptoms.

Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada.

Background: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020.

Methods: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics.

A systematic review of the prevalence of pathogenic or likely pathogenic germline variants in individuals with FOXO1 fusion-positive rhabdomyosarcoma.

Several cancer predisposition syndromes (CPS) are reported to predispose to rhabdomyosarcoma, most frequently in children with embryonal rhabdomyosarcoma. There are lingering questions over the role of CPS in individuals with alveolar rhabdomyosarcoma (ARMS), which are frequently driven by FOXO1 fusion oncoproteins. We conducted a systematic review to identify patients with FOXO1 fusion-positive ARMS (FP-ARMS) who underwent germline DNA sequencing.

Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes.

Background: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation.

Multicenter real-world experience of the clinical efficacy and tolerance of pazopanib in high-risk pediatric solid tumors (PazoPed).

Pazopanib, a receptor tyrosine kinase inhibitor, exhibits anti-tumor activity in adult bone and soft-tissue sarcomas (STS), but has not yet been approved for pediatric tumors. The primary objective was to evaluate pazopanib efficacy when used alone or in combination with topotecan. This real-world multicenter retrospective study included patients with solid tumors, aged 25 years or less at the time of initial diagnosis, treated with pazopanib outside of a clinical trial.

The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations.

We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset.

The Scottish RD survey 10 years on: the increasing incidence of retinal detachments.

Background: The Scottish RD Survey reported an incidence of 12.05/100,000/yr in 2009. Data published from Denmark recently confirmed a 50% increase in RD presentations over the last 16 years.

Neuroectodermal elements are part of the morphological spectrum of DICER1-associated neoplasms.

Many sarcomas with DICER1 pathogenic variants (PVs) exhibit a characteristic morphology, including a subepithelial layer of malignant mesenchymal cells, areas of rhabdomyoblastic differentiation and cartilaginous and/or osseous elements. We report 5 DICER1-associated neoplasms (1 moderately to poorly differentiated Sertoli Leydig cell tumour and 4 sarcomas) containing variable amounts of neuroectodermal elements. The neoplasms predominantly involved or were in close proximity to the female genital tract (ovary, uterine corpus, abdominal and pelvic cavity) and occurred in females aged 14 months to 54 years.

Medulloblastoma and Cowden syndrome: Further evidence of an association.

Cowden syndrome (CS) is an autosomal dominant hamartoma and tumor predisposition syndrome caused by heterozygous pathogenic germline variants in in most affected individuals. Major features include macrocrania, multiple facial tricholemmomas, acral and oral keratoses and papillomas, as well as mammary, non-medullary thyroid, renal, and endometrial carcinomas. Lhermitte-Duclos disease (LDD), or dysplastic gangliocytoma of the cerebellum, is the typical brain tumor associated with CS; the lifetime risk for LDD in CS patients has been estimated to be as high as 30%.

Companion Tumor Sequencing to Assess the Clinical Significance of Germline Sequencing in Children With Cancer.

This case-control study assesses the clinical significance of germline sequencing in children with cancer.

Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors.

Purpose: Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation.

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.

Patients And Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium.

Von Hippel-Lindau disease and rapidly progressing pheochromocytomas in siblings.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited condition with a predisposition to the development of a variety of tumors including pheochromocytomas. A number of cancer surveillance protocols for patients with VHL have been developed, all of which are based on expert opinion. We report a case of two brothers with a strong family history of VHL type 2 due to a pathogenic germline VHL variant, specifically, a surface missense substitution, with a rapidly progressive clinical course that both presented with a large adrenal mass.