An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence.

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.

Palliative radiotherapy: survival prognostic factors - single-centre retrospective cohort study.

OBJECTIVE: Patients with non-curative malignancy can receive palliative radiotherapy (PR) to alleviate symptoms. However, choosing the right patient to receive PR can be challenging, as some patients may not survive long enough to gain benefit. This study aims to identify prognostic factors for overall survival (OS) and 30-day mortality (30DM) following PR and to test these in a real-world cohort. METHOD: A retrospectively collected data set of all adults completing PR between 1 August 2018 and 31 December 2018 at a single centre (n=214, Southend University Hospital NHS Foundation Trust, UK) was used to test prognostic factors. Factors such as demographics, tumour primary, treatment area, fractionation regime, performance status (PS), progressive disease (PD), opioid or steroid use and haemoglobin level, as well as overall survival, were collected. Cox regression was used to examine survival predictors, and logistic regression was used to determine the predictive strength of factors for 30DM. RESULTS: Overall 30DM was 14%. There was significantly worse survival in patients with poor PS (HR 1.2406, 95% CI 0.94 to 1.64. p=0.01). Patients with PS 3 had a median OS of 75 days and were more likely to experience 30DM (OR 6.2, 95% CI 1.226 to 45.42, p=0.03). Patients with PD outside of the radiation field (46%, 30 out of 65 documented) had significantly worse OS (HR 5.24, 95% CI 2.19 to 12.5, p<0.001). CONCLUSION: Poor PS and PD were prognostic of OS and 30DM. Future work should include validation with a prospectively collected cohort.