Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC. METHODS: PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS). RESULTS: Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively. CONCLUSION: Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.

Assessing Circulating Tumour DNA (ctDNA) as a Biomarker for Anal Cancer Management: A Systematic Review.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Neo-adjuvant Vismodegib followed by radiation in locally advanced basal cell carcinoma.

Basal cell carcinomas occur in up to 39% of Caucasian men and 28% of women. Rarely it can present a management dilemma in patients with neglected locally advanced disease of large dimension or involvement of critical structures. The Hedgehog pathway is constitutively active in almost all basal cell carcinomas and patients with Naevoid Basal Cell Carcinoma Syndrome have germline mutations in the Patched tumor suppressor gene, a Hedgehog pathway component, on chromosome 9q. This case describes an elderly patient with an untreated sporadic Basal cell carcinoma whose dimensions precluded local management approaches. The Hedgehog pathway inhibitor Vismodegib had a dramatic response allowing definitive treatment to be pursued.

Survival of childhood and adolescent/young adult (AYA) cancer patients in Ireland during 1994-2013: comparisons by age.

BACKGROUND: Some studies indicate that survival of adolescents and young adults (AYA) with cancer may be inferior to that of younger children with similar cancers, possibly related (in part) to differences in access to centralized or standardized treatment. AIMS: This study aims to evaluate differences in survival for AYA patients when compared with paediatric patients treated in Ireland over a 20-year time period. METHODS: This study compares relative survival for patients diagnosed in Ireland at ages 0-15 (paediatric group) and 16-24 (AYA group) during 1994-2013, followed to the end of 2014, for cancers defined by the International Classification of Childhood Cancer (ICCC) (Third Edition) group or subgroup. Five-year relative survival estimates, and excess hazard ratios (EHR) comparing excess mortality associated with a cancer diagnosis among AYA with that in the paediatric group, are presented. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. RESULTS: Significantly higher excess mortality was found for AYA with leukaemias, lymphomas, astrocytomas, malignant bone tumours, and Ewing and related bone sarcomas, soft tissue sarcomas and 'other/unspecified' epithelial cancers, rhabdomyosarcomas, and 'other and unspecified' carcinomas. In contrast, lower excess mortality was found in the AYA group for all cancers and intracranial/intraspinal tumours, and for gliomas other than astrocytomas or ependymomas. Comparing 1994-2003 and 2004-2013 cohorts, age-related survival differences narrowed for lymphoid leukaemias, but widened for all cancers combined and intracranial/intraspinal tumours combined. Centralization of services varied depending upon cancer subtype, with leukaemias, CNS tumours and bone sarcomas most centralized. Within these, improvements in survival for leukaemias and CNS tumours have been seen for the AYA population. CONCLUSIONS: Reasons for age-related survival differences, and differences in time-trend by age group, are not clear. The significant narrowing of survival differences by age in more recent years for lymphoid leukaemias reflects a more marked recent increase in survival among AYA. More work is required to explain and improve other age-related survival differences.