A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.

Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC.

Differences in Attitudes and Barriers Towards Advance Care Planning Amongst Ischemic Heart Disease Patients: A Cross-Sectional Study.

OBJECTIVES: Perceptions towards advanced care planning (ACP) amongst individuals with Ischemic Heart Disease before or after a life-threatening Acute Myocardial Infarction event is underexamined and could impact the appropriate timing for ACP advocacy. This cross-sectional study assessed awareness and intentions regarding ACP in individuals with Ischemic Heart Disease, both before and after an Acute Myocardial Infarction, and explored the motivating effect of a near-fatal Acute Myocardial Infarction event on its engagement. METHODS: This study was conducted from 24 August 2021 through 13 March 2023, whereby patients were administered a one-time questionnaire with no follow-up required. Patients with either chronic Ischemic Heart Disease (group A) or a recent Acute Myocardial Infarction event (group B) were recruited from the outpatient National University Heart Centre, Singapore. RESULTS: 101 patients (n = 51 for Group A, n = 50 for Group B) were recruited. Mean age (SD) was 59 (10.5) years and 84 were male (83.2%). Between both groups, patients in group B reported significantly higher scores on 'Lack of information' and 'Self-efficacy' domains, and had no ACP awareness nor plans of doing an ACP compared to group A. ACP awareness was the sole significant predictor of intentions of doing an ACP in the final regression model (P < .05). CONCLUSIONS: Interestingly, this study suggests that surviving a potentially life-threatening heart condition did not result in higher intention of doing an ACP. Thus, advocacy of ACP in the community should simply start by raising awareness levels widely and may not need to be focused on individuals' state of health.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Insights from an Exploratory Retrospective Cohort Study: Are Face-to-Face Follow-Up Consultations after Colonoscopy a Thing of the Past?

BACKGROUND: Colonoscopy is a commonly performed procedure, but most patients will not actually be found with colorectal cancer. Subsequent face-to-face consultations to explain post-colonoscopy findings are common despite the time and cost-saving benefits of teleconsultation, especially in a post-COVID-19 era. This exploratory retrospective study examined the proportion of post-colonoscopy follow-up consultations that could have been converted to teleconsultation within a tertiary hospital in Singapore. METHODS: A retrospective cohort of all patients who underwent colonoscopy in the institution from July to September 2019 was identified. All follow-up face-to-face consultations related to the index colonoscopy from the scope date to 6 months post-colonoscopy were traced. Clinical data relevant to the index colonoscopy and these consultations were extracted from electronic medical records. RESULTS: The cohort consisted of 859 patients (68.5% male, age range: 18-96 years). Of these, 15 (1.7%) had colorectal cancer, but the majority (n = 643, 74.9%) were scheduled for at least one post-colonoscopy visit - a total of 884 face-to-face clinical visits. The final sample was 682 (77.1%) face-to-face post-colonoscopy visits that did not involve any procedures performed or indicated the need for any subsequent follow-up. CONCLUSION: If such "unnecessary" post-colonoscopy consultations exist within our institution, then similar situations possibly occur elsewhere. As COVID-19 continues to periodically tax healthcare systems worldwide, preservation of resources will remain integral alongside quality standards of routine patient care. There is a need for detailed analyses and modeling to hypothesize potential savings by also considering the start-up and maintenance costs of switching to a teleconsultation-dominated system.