ONCOTHESIS

Optimising treatment and follow-up of patients with bladder cancer: Risk stratification and biomarkers

SUMMARY

Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are at risk for disease progression, which encompasses significant treatment-related and cancer-specific morbidity and mortality. Therefore, stratification of patients is important to identify patients that are at risk for progression of disease. However, current risk stratification lacks accuracy to identify which patients will progress and ultimately succumb to their disease. This PhD thesis focused on identifying prognostic biomarkers to optimise risk stratification of patients with NMIBC. The tumour immune microenvironment (TIME) and markers for basal and luminal differentiation were analysed using an immunohistochemical (IHC) panel in patients with high-risk T1 NMIBC. Interestingly, we identified fibroblast activation protein-α (FAP) expression as a prognostic marker for progression in highrisk NMIBC. FAP is a marker for cancer-associated fibroblasts (CAF), which play an important role in the TIME.

(BELG J MED ONCOL 2024;18(1):29–32)

Novel strategies in the management of high-risk and oligometastatic prostate cancer

SUMMARY

The aim of this thesis was to assess the impact of intensive hormonal therapy prior to radical prostatectomy in high-risk prostate cancer (PCa) in order to optimise the outcome of this patient population. Next, the recurrence patterns of PCa patients with prostate-specific antigen (PSA) relapse following localised therapy were assessed using novel imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT). Moreover, the safety and oncological outcomes of PCa men with oligometastatic recurrence (1–5 lesions) following localised therapy treated with metastasis-directed therapy were investigated. Lastly, the safety and efficacy of radium-223 in men with PSA relapse following localised therapy without visible lesions on PSMA PET/CT were assessed.

(Belg J Med Oncol 2023;17(7):267–70)

Improving dysphagia care in head and neck cancer patients treated with radiotherapy

SUMMARY

Dysphagia is a common and widely reported complication during and after radiotherapy (RT) for head and neck cancer (HNC), affecting quality of life (QoL). Research concerning the use of prophylactic swallowing exercises (PSE) is growing, and positive effects on muscle composition, swallowing function and QoL have already been demonstrated. However, low adherence to PSE undermines the beneficial effects. The PRESTO program, an optimised, patient-tailored and evidence-based prophylactic swallowing program augmented with adherence-improving measures was, therefore, developed. Different general but also more specific methods to increase adherence were considered. The way the PSE program was delivered depended on the treatment group (paper-, app- or therapist-supported PSE). After implementing PRESTO in 148 oropharyngeal cancer patients treated at four different hospitals in Flanders, results showed that the adherence towards PSE was the highest in the therapist-supported group. Face-to-face therapy may, thus, solve the problem of low adherence rates. In addition, it was observed that only patients practising at a high frequency (≥75% of the prescribed exercises) would achieve positive effects of the PSE on swallowing function and muscle strength. The results of this PhD research are clinically relevant and contribute to better supportive care in patients with HNC.

(Belg J Med Oncol 2023;17(6):236–8)

Exploiting genomic vulnerabilities in lung cancer for therapeutic targeting

GRAPHICAL ABSTRACT

(Belg J Med Oncol 2023;17(4):132–4)

Simply the B(r)east: Endothelial cell heterogeneity in health and disease

SUMMARY

This thesis aimed to unveil new insights into breast cancer (BC) vasculature, since this could potentially have a large clinical impact. To do so, single-cell RNA-sequencing was performed on the breast cancer vasculature and tumour microenvironment. The analysis revealed novel interactions between immune cells and endothelial cells (ECs), and identified a capillary EC subtype, called lipid processing ECs (LIPECs), expressing genes regulated by PPAR-γ. Retrospectively, this study uncovered breast cancer-specific clinical benefits of PPAR-γ agonist (metformin) treatment, positively correlated with LIPEC abundance. In conclusion, these findings unravelled heterogeneity in breast ECs, and raise the question of whether targeting specific EC subtypes is a potential avenue for BC treatment.

(Belg J Med Oncol 2023;17(3):88–90)

Immune cell and extracellular vesicle-based biomarkers for gynaecologic cancers

SUMMARY

Immune checkpoint blockade has shown great potential in oncology. However, only a fraction of patients benefits from this therapy. Furthermore, severe immune-related adverse events occur in a part of the patients, and financial toxicity cannot be underestimated. It is therefore important to develop predictive biomarkers to differentiate responders from non-responders. Tumour tissue samples offer a large amount of information as anti-tumour immunity is regulated through multiple factors in the tumour microenvironment. The potential of tumour-infiltrating immune cells was investigated to predict response to therapy and survival. In contrast to tissue biopsies, liquid biopsies allow for collection in a less invasive manner, allow for repetitive sampling during therapy, and offer information on all cancer cells in the tumour as well as metastases at distinct locations in the body. Extracellular vesicles (EVs) present in the circulation are a spatiotemporal fingerprint of the cell of origin. Therefore, EV-derived information has the potential to be used for diagnosis, prognosis, treatment selection and evaluating treatment response. However, the clinical application of EVs is currently hampered by a lack of sensitive, high-throughput and fast EV analysis techniques.

(BELG J MED ONCOL 2023;17(2):63–5)

Patient selection strategies throughout the renal cell carcinoma disease spectrum

SUMMARY

The present doctoral thesis manuscript aims to inform disease prognosis and guide therapeutic decision-making at all stages of the renal cell carcinoma disease spectrum. Novel imaging methods to improve pre-surgical characterisation of renal masses were developed, as well as prediction models for the estimation of postoperative renal function. Next, four molecular subtypes of clear cell renal cell carcinoma were described, their underlying disease biology and their implications in both the localised and metastatic settings. Moreover, the potential candidates for cytoreductive surgery were described, as well as the morbidity accompanying such procedures in the metastatic setting.

(BELG J MED ONCOL 2023;17(1):31–2)