PhD Defence Ellis Slotman | Balancing burden and benefit in advanced cancer: real-world insights into treatment considerations, patterns and outcomes

Balancing burden and benefit in advanced cancer: real-world insights into treatment considerations, patterns and outcomes

Ellis Slotman is a PhD student in the Department of Health Technology and Services Research. (Co)Promotors are prof.dr. S. Siesling from the Faculty of Behavioural, Management and Social Sciences, prof.dr. Y.M. van der Linden from Leiden University Medical Center and dr. N. Raijmakers and dr. H.P. Fransen from the Netherlands Comprehensive Cancer Organisation.

For patients with advanced cancer, cure is often no longer possible, and the focus shifts towards quality of life, symptom burden, and improving prognosis. Treatment decision-making is complex and frequently based on evidence that is not fully representative of everyday clinical practice. In this thesis, we use real‑world data to provide insight into treatment patterns, outcomes, and end‑of‑life care in routine clinical practice.

Part 1 focused on treatment patterns and outcomes. At the population level, the studies showed that median survival of patients with metastatic cancer increased only modestly over time, despite the introduction of new systemic therapies. Only a small minority of all patients with metastatic cancer (15%) received immunotherapy or targeted therapy. Within these treatment groups, relatively long survival outcomes were observed in some patients, but with substantial variation. In patients with metastatic bladder cancer, palliative systemic treatment often could not be continued according to guideline recommendations, and treatment modifications such as dose reductions were frequently required. For patients with advanced gastric or oesophageal cancer, patient or family preference was an important reason to refrain from systemic treatment. In addition, patients with metachronous metastatic breast cancer presented with less favorable disease characteristics and had poorer survival outcomes compared to patients with synchronous metastases. Beyond the existing complexity of treatment decision‑making in advanced cancer, the COVID‑19 pandemic introduced additional challenges. However, the impact of the pandemic on the initial treatment of metastatic cancer was shown to be limited: treatment patterns remained largely stable, although patients started initial treatment slightly earlier. In radiotherapy for bone metastases, hypofractionation was applied more frequently during the pandemic, although substantial variation between centers persisted.

Part 2 addressed end‑of‑life care. Pain was highly prevalent in the last week of life of patients with cancer: more than 80% experienced pain, and 35% reported severe pain. Structured symptom monitoring (e.g. using VAS/NRS) was associated with better pain relief. During the COVID‑19 pandemic, the rate of potentially inappropriate end‑of‑life care decreased, mainly due to fewer hospitalizations, ICU admissions, and in‑hospital deaths. In addition, potentially inappropriate end‑of‑life care was found to be associated with negative consequences for the well‑being of relatives.