Long-term outcome of "Sandwich" chemo-PRRT: a novel treatment strategy for metastatic neuroendocrine tumors with both FDG- and SSTR-avid aggressive disease.

objectiveThe primary aims of this study were to evaluate the long-term outcome of a "sandwich chemo-PRRT (SCPRRT)" regimen with regard to therapeutic response rate, progression-free survival (PFS), and overall survival (OS) rates in metastatic neuroendocrine tumors (NETs) with both somatostatin receptor (SSTR)- and fluorodeoxyglucose (FDG)-avid aggressive disease. Additionally, health-related quality of life (HRQoL) scales, clinical toxicity, and association of PFS and disease control rate (DCR) with various variables were also evaluated. MATERIALS AND

methodsA total of 38 patients of the aforementioned cohort, who received SCPRRT (at least 2 cycles of each PRRT and chemotherapy) at our institute between January 2012 and December 2018, were included and analyzed in this retrospective study. Between two cycles of

resultsResponse (complete response and partial response) to SCPRRT was seen in 28 patients (73%), 15 patients (39%), and 16 patients (42%) on symptomatic, biochemical, and molecular imaging response evaluation criteria respectively. A total of 17 patients (45%) had anatomical imaging response with DCR of 84% based upon the RECIST 1.1 criteria. Pre-therapy mean ECOG and KPS was 2.0 and 68, which changed to 1.0 and 75 respectively following SCPRRT. Long-term follow-up data was available and ranged from 12 to 65 months after the first SCPRRT. Median PFS and OS were not reached at a median follow-up of 36 months. An estimated PFS rate of 72.5% and OS rate of 80.4% was found at 36 months. Longer PFS was dependent upon high SSTR uptake and number of CAPTEM cycle (≥ 7 cycles), absence of skeletal metastasis, and no previous external beam radiotherapy (EBRT) exposure with significant P value. Higher DCR was dependent upon absence of skeletal metastasis with significant P value. SCPRRT was tolerated well with none developing grade 4 hematotoxicity and nephrotoxicity of any grade. Anemia (grade 3), thrombocytopenia (grade 3), and leukopenia (grade 3) were noticed in 1 patient (2.5%), 2 patients (5%), and 1 patient (2.5%) respectively in this study.

conclusionThus, favorable response rates with effective control of symptoms and longer PFS and OS without high-grade or life-threatening toxicities were important observations in the present study following SCPRRT in NET patients with aggressive, both FDG- and SSTR-avid, metastatic progressive disease. The study results indicate the potential role of "sandwich chemo-PRRT" in future therapeutic algorithms of aggressive, both SSTR- and FDG-positive subset of neuroendocrine tumors.