THE ROLE OF LUTETIUM-177 IN THE TREATMENT OF METASTATIC GASTROENTEROPANCREATIC TUMORS

Abstract

Purpose The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been increasing over recent decades. Lutetium therapy has demonstrated benefit towards quality of life (QoL) overall in patients with metastatic GEP-NETs. However, factors influencing individual response to 177Lu-DOTATATE with regards to QoL, and methods for easy integration of QoL monitoring into clinical practice are not yet well understood. This work seeks to identify optimal methods for QoL assessment and prognostic factors for QoL response in patients with progressive GEP-NETs treated with 177Lu-DOTATATE. Methods This study was conducted as part of the Phase II open label clinical trial at the Cross Cancer Institute in Edmonton. Treatment consisted of an induction phase of 5.55 GBq administered at four treatments, 10 weeks apart. QoL over 177Lu-DOTATATE treatment was assessed with EORTC QLQ-C30, GI.NET-21 and ESAS-r at baseline and subsequent to each treatment. Planned analysis of change in QoL by corresponding assessment method and factors related to change in QoL was completed in all patients with GEP-NETs. Repeated measures ANOVA was performed to assess QoL change and purposeful logistic regression for identification of prognostic factors. Results In total 85 patients met inclusion criteria. Both EORTC and ESAS-r demonstrated maintained overall quality of life. EORTC demonstrated statistically and clinically significant improvement in insomnia, GI and endocrine symptoms. ESAS-r demonstrated statistically but no clinically significant improvement in insomnia, anxiety and emotional functioning. ii In the final regression model for prognostic factors for QoL a statistically significant correlation was demonstrated between global health score at baseline and time from diagnosis to treatment initiation with 177Lu-DOTATATE. The presence of metastatic disease was marginally statistically significant with regards to change in global health score after 177Lu-DOTATATE induction therapy. Conclusions 177Lu-DOTATATE is not only effective in improving PFS for patients with metastatic GEP-NETs but also impacts overall quality of life. Consideration in treatment initiation in this palliative setting should include potential impact to patient QoL as the impact of 177Lu-DOTATATE therapy on QoL improvement appears to decrease in correlation to delay in 177Lu-DOTATATE treatment. To monitor changes in QoL during treatment all assessment tools have inherent benefits and limitations which must be considered in clinical use. ESAS-r provides a quick and easy to interpret tool; however, it is not NET specific and as such may not be as sensitive in this population. The EORTC assessment questionnaires better reflect QoL in the NET population. Modifications or use of computer integration could be considered to facilitate clinical incorporation.