Daniel Molin’s projects on clinical and translational research in lymphoma

Background

Lymphomas comprise a heterogeneous group of malignancies with varying degrees of aggressiveness and prognosis. One such entity is Hodgkin lymphoma. The majority of individuals affected by Hodgkin lymphoma are young, and most are cured; however, treatment is associated with a risk of long-term adverse effects.

There is a lack of knowledge regarding the effects of modern radiotherapy and early markers predicting the risk of treatment-related toxicity. Physical exercise during treatment has previously been shown to have beneficial effects. Proton therapy is a relatively new technique in this context and has the potential to reduce radiation exposure to healthy tissues.

Epidemiology – survival, risk of relapse and adverse effects

The research group investigates relative survival in Hodgkin lymphoma, risk of relapse, and the toxicity profile associated with more contemporary treatments than those previously studied. We further examine the incidence and underlying causes of specific adverse effects that we have previously described.

In addition to radiotherapy, we also study the optimal choice of systemic therapy, considering both efficacy and toxicity. Besides classical Hodgkin lymphoma, we also examine nodular lymphocyte predominant Hodgkin lymphoma (NLPHL).

Genetic alterations and circulating tumour DNA

We investigate genetic alterations, primarily single nucleotide polymorphisms, in patients treated with large-field radiotherapy and cardiotoxic chemotherapy, with and without cardiac and other adverse effects. We also analyse circulating tumour DNA (ctDNA; liquid biopsy) to facilitate the translation of genetic insights into clinical practice.

Proteomic profiles related to inflammation and adverse effects

Within the group, we study protein expression using Olink™ panels (approximately 1,500 proteins) and relate these findings to toxicity, inflammation, prognosis, and disease aetiology. In particular, we investigate the relationship between the degree of inflammation in Hodgkin lymphoma and proteomic profiles. Preliminary results indicate substantial differences between patient groups with varying levels of inflammation.

We also examine associations between proteomic patterns and long-term adverse effects. A validation cohort encompassing all lymphoma subtypes is currently being analysed. Our proteomics projects are part of a large pan-lymphoma collaboration involving multiple research groups, in which we are actively engaged.

PET/CT

We have previously published, for example, comparisons between diffusion-weighted MRI and FDG PET/CT in collaboration with Håkan Ahlström’s group in radiology. We now plan to examine PET imaging data from a large international trial. These data will be analysed using advanced AI-based techniques developed by the Ahlström/Kullberg group.

The PRO-Hodgkin project

Our group is conducting an investigator-initiated clinical trial in which patients, following standard chemotherapy, are treated with proton therapy – a novel treatment modality in this context – at the Skandion Clinic. PRO-Hodgkin is largely funded by the Swedish Cancer Society and includes patients from across the country.

Impact of physical exercise

We are participating in a randomized trial – LYMfit – where we examine the impact of physical exercise 2–5 years after lymphoma diagnosis. A joint PhD student has been appointed.

International clinical trials

We are actively involved in international clinical trials in lymphoma, particularly Hodgkin lymphoma. Examples of successful studies include RATHL, several KEYNOTE trials, BVB (B-CAP), and HD21.