Machine learning based local recurrence prediction in colorectal cancer using polarized light imaging.

Significance: Current treatment for stage III colorectal cancer (CRC) patients involves surgery that may not be sufficient in many cases, requiring additional adjuvant systemic therapy. Identification of this latter cohort that is likely to recur following surgery is key to better personalized therapy selection, but there is a lack of proper quantitative assessment tools for potential clinical adoption. Aim: The purpose of this study is to employ Mueller matrix (MM) polarized light microscopy in combination with supervised machine learning (ML) to quantitatively analyze the prognostic value of peri-tumoral collagen in CRC in relation to 5-year local recurrence (LR). Approach: A simple MM microscope setup was used to image surgical resection samples acquired from stage III CRC patients. Various potential biomarkers of LR were derived from MM elements via decomposition and transformation operations. These were used as features by different supervised ML models to distinguish samples from patients that locally recurred 5 years later from those that did not. Results: Using the top five most prognostic polarimetric biomarkers ranked by their relevant feature importances, the best-performing XGBoost model achieved a patient-level accuracy of 86%. When the patient pool was further stratified, 96% accuracy was achieved within a tumor-stage-III sub-cohort. Conclusions: ML-aided polarimetric analysis of collagenous stroma may provide prognostic value toward improving the clinical management of CRC patients.

Mueller matrix polarization parameters correlate with local recurrence in patients with stage III colorectal cancer.

The peri-tumoural stroma has been explored as a useful source of prognostic information in colorectal cancer. Using Mueller matrix (MM) polarized light microscopy for quantification of unstained histology slides, the current study assesses the prognostic potential of polarimetric characteristics of peri-tumoural collagenous stroma architecture in 38 human stage III colorectal cancer (CRC) patient samples. Specifically, Mueller matrix transformation and polar decomposition parameters were tested for association with 5-year patient local recurrence outcomes. The results show that some of these polarimetric parameters were significantly different (p value < 0.05) for the recurrence versus the no-recurrence patient cohorts (Mann-Whitney U test). MM parameters may thus be prognostically valuable towards improving clinical management/treatment stratification in CRC patients.

Polarimetric biomarkers of peri-tumoral stroma can correlate with 5-year survival in patients with left-sided colorectal cancer.

Using a novel variant of polarized light microscopy for high-contrast imaging and quantification of unstained histology slides, the current study assesses the prognostic potential of peri-tumoral collagenous stroma architecture in 32 human stage III colorectal cancer (CRC) patient samples. We analyze three distinct polarimetrically-derived images and their associated texture features, explore different unsupervised clustering algorithm models to group the data, and compare the resultant groupings with patient survival. The results demonstrate an appreciable total accuracy of ~ 78% with significant separation (p < 0.05) across all approaches for the binary classification of 5-year patient survival outcomes. Surviving patients preferentially belonged to Cluster 1 irrespective of model approach, suggesting similar stromal microstructural characteristics in this sub-population. The results suggest that polarimetrically-derived stromal biomarkers may possess prognostic value that could improve clinical management/treatment stratification in CRC patients.

Bio-acoustic signaling; exploring the potential of sound as a mediator of low-dose radiation and stress responses in the environment.

OBJECTIVES: This commentary reviews and evaluates the role of sound signals as part of the infosome of cells and organisms. Emission and receipt of sound has recently been identified as a potentially important universal signaling mechanism invoked when organisms are stressed. Recent evidence from plants, animals and microbes suggests that it could be a stimulus for specific or general molecular cellular stress responses in different contexts, and for triggering population level responses. This paper reviews the current status of the field with particular reference to the potential role of sound signaling as an immediate/early bystander effector (RIBE) during radiation-induced stress. CONCLUSIONS: While the chemical effectors involved in intercellular and inter-organismal signaling have been the subject of intense study in the field of Chemical Ecology, less appears to be known about physical signals in general and sound signals in particular. From this review we conclude that these signals are ubiquitous in each kingdom and behave very like physical bystander signals leading to regulation of metabolic pathways and gene expression patterns involved in adaptation, synchronization of population responses, and repair or defence against damage. We propose the hypothesis that acoustic energy released on interaction of biota with electromagnetic radiation may represent a signal released by irradiated cells leading to, or complementing, or interacting with, other responses, such as endosome release, responsible for signal relay within the unirradiated individuals in the targeted population.

Toward a quantitative method for estimating tumour-stroma ratio in breast cancer using polarized light microscopy.

The tumour-stroma ratio (TSR) has been explored as a useful source of prognostic information in various cancers, including colorectal, breast, and gastric. Despite research showing potential prognostic utility, its uptake into the clinic has been limited, in part due to challenges associated with subjectivity, reproducibility, and quantification. We have recently proposed a simple, robust, and quantifiable high-contrast method of imaging intra- and peri-tumoural stroma based on polarized light microscopy. Here we report on its use to quantify TSR in human breast cancer using unstained slides from 40 patient samples of invasive ductal carcinoma (IDC). Polarimetric results based on a stromal abundance metric correlated well with pathology designations, showing a statistically significant difference between high- and low-stroma samples as scored by two clinical pathologists. The described polarized light imaging methodology shows promise for use as a quantitative, automatic, and standardizable tool for quantifying TSR, potentially addressing some of the challenges associated with its current estimation.

An investigation into neutron-induced bystander effects: How low can you go?

Neutron radiation is very harmful to both individual organisms and the environment. A n understanding of all aspects of both direct and indirect effects of radiation is necessary to accurately assess the risk of neutron radiation exposure. This review seeks to review current evidence in the literature for radiation-induced bystander effects and related effects attributable to neutron radiation. It also attempts to determine if the suggested evidence in the literature is sufficient to justify claims that neutron-based radiation can cause radiation-induced bystander effects. Lastly, the present paper suggests potential directions for future research concerning neutron radiation-induced bystander effects. Data was collected from studies investigating radiation-induced bystander effects and was used to mathematically generate pooled datasets and putative trends; this was done to potentially elucidate both the appearance of a conventional trend for radiation-induced bystander effects in studies using different types of radiation. Furthermore, literature review was used to compare studies utilizing similar tissue models to determine if neutron effects follow similar trends as those produced by electromagnetic radiation. We conclude that the current understanding of neutron-attributable radiation-induced bystander effects is incomplete. Various factors such as high gamma contamination during the irradiations, unestablished thresholds for gamma effects, different cell lines, energies, and different dose rates affected our ability to confirm a relationship between neutron irradiation and RIBE, particularly in low-dose regions below 100 mGy. It was determined through meta-analysis of the data that effects attributable to neutrons do seem to exist at higher doses, while gamma effects seem likely predominant at lower dose regions. Therefore, whether neutrons can induce bystander effects at lower doses remains unclear. Further research is required to confirm these findings and various recommendations are made to assist in this effort. With these recommendations, we hope that research conducted in the future will be better equipped to explore the indirect effects of neutron radiation as they pertain to biological and ecological phenomena.