Monitoring of neuroendocrine tumor patients undergoing systemic therapies

Sammanfattning: Monitoring of neuroendocrine tumor (NET) patients undergoing systemic therapies is troublesome as biomarkers capable of detecting tumor responses have been difficult to establish. Changes in the sum of target lesion diameters are used to evaluate the effects of therapy according to the response evaluation criteria in solid tumors (RECIST 1.1). However, as NETs tend to stabilize or increase in size when responding to therapies, monitoring based on changes in tumor diameters is often ineffective.The overall aim of these doctoral studies was to investigate novel methods for therapy monitoring in NET patients undergoing systemic therapies.In patients with pancreatic NETs (PanNETs) who underwent Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE at Uppsala University Hospital (n=151), we investigated if arterial-phase tumor attenuation and contrast-enhancement in the liver metastases on computed tomography (CT) changed during PRRT (Paper I).Tumor growth rate (TGR) allows for quantitative assessment of tumor dynamics expressed as percentage per month. In the same cohort as described above, TGR was calculated before and during/after PRRT (Paper II).While 68Ga-DOTA-somatotstatin analog (SSA) PET/CT is essential in the evaluation of NET patient eligibility for PRRT, temporal changes in the tumor uptake of 68Ga-DOTA-SSA have not been shown to reflect PRRT outcome. Tumor-to-blood (TBR) ratio may be closer correlated than SUV to the net influx rate (Ki). The institutional database of the University Hospital in Essen was screened for NET patients, who had undergone at least two cycles of PRRT and 68Ga-DOTA-SSA PET/CT. TBR and tumor-spleen ratio (TSR) were calculated in up to nine lesions per patient (Paper III).Data on imaging were investigated for possible associations with outcome parameters such as progression-free survival and overall survival (Papers I-III).46 PanNET patients with data on Ki-67 from at least two biopsies (Botling et al. 2019) at Uppsala University Hospital were screened for inclusion to describe TGR in PanNET patients. TGR was calculated to elucidate if changes in tumor grade may be reflected in changes in TGR. (Paper IV).In summary, the thesis investigates tools based on morphologic and functional imaging for monitoring of NET patients undergoing systemic therapies.