Monitoring the effect of anti-cancer treatment in uro-oncological malignancies with molecular imaging

In the last decade, new therapies have changed the management of patients with metastatic renal cell carcinoma (mRCC) and metastatic castration resistant prostate cancer (mCRPC). Although new therapies have improved survival, drug response varies widely with some patients not responding to treatment. Unfortunately, traditional assessment of drug response with computed tomography (CT) has limitations, and novel biomarkers of treatment response are warranted in order to reduce unnecessary side-effects and costs. The general aim of this thesis was to identify imaging biomarkers that can help predict the treatment response in mRCC and mCRPC.

In the first study, metabolic changes of tumour lesions detected by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and CT (PET/CT) after 14 days of treatment predicted the progression-free (PFS) and overall survival (OS) in 32 patients. Metabolic response was assessed in several ways revealing that PET parameters measuring FDG uptake within a volume had stronger association to outcome than parameters based on single voxel analysis. In the second study, the benefit of repeated 11C-acetate PET/CT was evaluated retrospectively to assess response in patients with mCRPC treated with abiraterone acetate. Potential association between 11C-acetate PET/CT, serum levels of prostate specific antigen (PSA), PFS and OS were investigated. 11C-acetate PET/CT predicted PFS and OS which may be of particular clinical interest in patients who do not exhibit a PSA response to treatment. In the third study, the maximal diameter of metastatic lesions originating from mRCC as determined by diffusion-weighted magnetic resonance imaging (DWI) were compared with the corresponding measurements on CT. These measurements appeared to be in close agreement warranting for a larger trial investigating the feasibility of employing DWI in clinical trials that follow the Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) guideline.

In conclusion, the novel imaging biomarkers evaluated here have the ability to predict response of mRCC and mCRPC to targeted therapies, but need to be validated in a larger setting before being implemented into the clinic.

List of scientific papers

I. Volumetric FDG-PET predicts overall and progression-free survival after 14 days of targeted therapy in metastatic renal cell carcinoma. Jacob Farnebo, Per Grybäck, Ulrika Harmenberg, Anna Laurell, Peter Wersäll, Lennart K Blomqvist, Anders Ullén and Per Sandström. BMC Cancer. 2014, 14:408.
https://doi.org/10.1186/1471-2407-14-408

II. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT. Jacob Farnebo, Agnes Wadelius, Per Sandström, Sten Nilsson, Hans Jacobsson, Lennart Blomqvist, Anders Ullén. Medicine. 2016, 95:31.
https://doi.org/10.1097/MD.0000000000004308

III. Measurements of metastatic renal cell tumours as determined by whole-body diffusion weighted imaging or computed tomography are in close concordance: a pilot study. Farnebo J, Suzuki C, Vargas R, Sandström P, Blomqvist L. [Manuscript]