Category: Research

Primary Care Research into Cancer(PRICAN)

What is PRICAN?

Cancer represents a significant public health challenge in Ireland. Forecasts also indicate a potential doubling of cancer diagnoses between 2010 and 2040, primarily due to an ageing population. 

In recent years, there has been a shift in cancer control strategies towards prioritising prevention and early diagnosis, as the most cost-effective long-term approach to cancer control.

The National Cancer Strategy explicitly calls for an expanded role for general practitioners (GPs) in managing the entire cancer continuum, from prevention and early diagnosis to treatment and ongoing survivor support.

Despite its increasing importance in cancer control, primary care research has historically received less funding compared to laboratory and hospital-based research.

Whilst screening enables early detection of some presymptomatic cancer, approximately 85% of cancers are diagnosed after the onset of symptoms . This fact underscores the importance of equipping primary care with robust clinical guidelines and efficient referral pathways. 

The anticipated rise in cancer incidence demands proactive measures to strengthen the Irish healthcare system. By recognising the critical role of primary care across the cancer care continuum, and adopting a strategic approach to investment in research, Ireland can develop and implement evidence-based policies and strategies. This approach will not only mitigate the impacts of increasing cancer incidence but also position Ireland at the forefront of innovative and effective cancer care.

https://prican.eu

The tumour histopathology “glossary” for AI developers

The applications of artificial intelligence (AI) and deep learning (DL) are leading to significant advances in cancer research, particularly in analysing histopathology images for prognostic and treatment-predictive insights.

However, effective translation of these computational methods requires computational researchers to have at least a basic understanding of histopathology. In this work, we aim to bridge that gap by introducing essential histopathology concepts to support AI developers in their research. 

Challenges and outlook

To be implemented into routine practice, an AI algorithm needs several indispensable properties, i.e.,

clinical relevance, high accuracy, rapid implementation, fast computation, and last but not least, user-friendliness.

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1012708#abstract0

EPI what?

Epigenetics: Is a way of influencing how our genome is regulated without the DNA code itself being changed. Epigenetics can determine when genes are turned on and off (also referred to as gene expression), and which proteins are produced as a result. It can even control the structure of the genome, relaxing the tightly packed chromosomes to allow the factors which control gene expression access to the genes within.

One example of an epigenetic modification is methylation, which is associated with switching genes off. Here, a chemical called a methyl group attaches to a region near the start of a gene and prevents it from being switched on.

Lynch syndrome also illustrates the significance of the epigenetic component in cancer development. Inactivation of tumor suppressor genes by epigenetic mechanisms is an acquired property of many tumors developing in Lynch syndrome.

https://www.genomicseducation.hee.nhs.uk/education/core-concepts/what-is-epigenetics/

Neoadjuvant immunotherapy for locally advanced/metastatic mismatch repair deficient colorectal cancer: a two-year institutional experience.

Loss of MMR functioning, termed MMR deficiency (MMRd), leads to microsatellite instability (MSI),2 a hypermutated phenotype, and increased cancer susceptibility. Lynch syndrome patients are at an increased risk for a number of different malignancies, but most commonly develop colorectal and endometrial cancer.

Findings add to the growing body of evidence in support of neoadjuvant immune checkpoint inhibitors for MMRd CRC, and highlight the importance of screening all CRC for MSI-H/ MMRd.

Influence of preoperative Lynch syndrome diagnosis on surgery in patients with colorectal cancer.

Lynch Syndrome (LS) can guide surgery for colorectal cancer (CRC), particularly for MLH1/MSH2 carriers, who may benefit from extended procedures: total colectomy (TC) or total proctocolectomy (TP).Investigated timing of germline genetic testing (GGT) and surgical approach in patients (pts) with LS and CRC.

Conclusions: GGT performed pre-surgery for a new diagnosis of CRC was more likely to result in extended procedures, especially in MLH1/MSH2/EPCAM carriers. More data in RC is needed to better understand the influence of GGT on surgical approach.

https://meetings.asco.org/abstracts-presentations/241883

Young Onset Gastrointestinal Cancers: A needs analysis

The global incidence of Young Onset ( YO) cancers diagnosed in adults under 50 years, is increasing for unknown reasons. 

This study(88 participants) assessed the holistic needs of these patients through a mixed methods approach.

Conclusions: This needs analysis highlights the importance of specialised clinical pathways for young onset GI cancer patients focusing on these unique and complex needs. Financial supports, conversations regarding sexual health/function, fertility preservation and psychosocial support are critical areas requiring structured intervention.

https://meetings.asco.org/abstracts-presentations/241255

“Much of our work around Lynch syndrome is preventing cancer before it starts”

Director of the Lynch Syndrome Center Shares his Personal Connection to Lynch Syndrome

VARIANT OF UNCERTAIN SIGNIFICANCE (VUS)

When analysis of a patient’s genome identifies a variant, but it is unclear whether that variant is actually connected to a health condition, the finding is called a variant of uncertain significance (abbreviated VUS).

In many cases, these variants are so rare in the population that little information is available about them. Typically, more information is required to determine if the variant is disease related. Such information may include more extensive population data, functional studies, and tracing the variant in other family members who have or do not have the same health condition.

AI and Machine Learning are poised to play a significant role in advancing Genetic Testing practices.

These study findings offer hope that further acceleration of VUS reduction is possible through advances in these rapidly evolving technologies. 

Conclusions and Relevance  In this cohort study of individuals undergoing genetic testing, the empirically estimated accuracy of pathogenic, likely pathogenic, benign, and likely benign classifications exceeded the certainty thresholds set by current VC guidelines, suggesting the need to reevaluate definitions of these classifications. The relative contribution of various strategies to resolve VUS, including emerging machine learning–based computational methods, RNA analysis, and cascade family testing, provides useful insights that can be applied toward further improving VC methods, reducing the rate of VUS, and generating more definitive results for patients.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825808

Cancer and Fatigue Go Together

Every cancer has different side effects depending on the type, which stage it is in, and the treatments given. But when 80/100% of the people report fatigue, we know this is an ongoing problem.

I hope I continue to find new research and training on this often overlooked and important side effect – perhaps the most devastating of all!

https://www.curetoday.com/view/cancer-and-fatigue-go-together

Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data

Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years).

The increase in early-onset colorectal cancer, previously seen predominately in high-income western countries, has now been documented in various economies and regions worldwide, marking it as a global phenomenon.

The global reach of this alarming trend calls for innovative tools to prevent and control cancers linked to nutritional attributes, physical inactivity, and excess bodyweight, which might be more challenging to address than the tobacco epidemic.

Educational efforts to increase awareness of the increase in the incidence of early-onset colorectal cancer and its unique symptoms, especially among primary care providers, would have far reaching effects in reducing delayed diagnoses and mortality.

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00600-4/fulltext