Interim analysis of a prospective validation of 2 blood-based genomic assessments (PPQ and NETest) to determine the clinical efficacy of (177)Lu-DOTATATE in neuroendocrine tumors Journal Article
| Authors: | Bodei, L.; Raj, N.; Do, R. K.; Mauguen, A.; Krebs, S.; Reidy-Lagunes, D.; Schöder, H. |
| Article Title: | Interim analysis of a prospective validation of 2 blood-based genomic assessments (PPQ and NETest) to determine the clinical efficacy of (177)Lu-DOTATATE in neuroendocrine tumors |
| Abstract: | Reliable biomarkers for neuroendocrine tumor (NET) management during peptide receptor radionuclide therapy (PRRT) are lacking. We validated the role of 2 circulating biomarkers: the PRRT prediction quotient (PPQ) as a predictive marker for response and the NETest as a monitoring biomarker. Furthermore, we evaluated whether tissue-based genetic alterations are effective in predicting progression-free survival (PFS). Methods: Data were prospectively collected on patients at the Memorial Sloan Kettering Cancer Center with 177Lu-DOTATATE-treated somatostatin receptor (SSTR)-positive gastroenteropancreatic and lung NETs (n = 67; median age, 66 y; 52% female; 42% pancreatic, 39% small-bowel; 78% grade 1 or 2). All cases were metastatic (89% liver) and had received 1-8 prior treatments (median, 3), including somatostatin analogs (91%), surgery (55%), or chemotherapy (49%). Treatment response included PFS. According to RECIST, version 1.1, responders had stable disease or a partial response (disease-control rate) and nonresponders had progression. Blood was collected before each cycle and at follow-up. Samples were deidentified and assayed and underwent masked analyses. The gene expression assays included RNA isolation, real-time quantitative polymerase chain reaction, and multialgorithm analyses. The PPQ (positive predicts a responder; negative predicts a nonresponder) at baseline was determined. The NETest (0-100 score) was performed. Statistics were analyzed using Mann-Whitney U testing (2-tailed) or Kaplan-Meier survival testing (PFS). In patients with archival tumor tissue, next-generation sequencing was performed through an institutional platform (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets). Results: Forty-one patients (61%) were responders. PPQ accurately predicted 96% (64/67). The hazard ratio for prediction was 24.4 (95% CI, 8.2-72.5). Twelve-month disease control was 97% for PPQ-positive patients versus 26% for PPQ-negative patients (P < 0.0001). Median progression-free survival was not reached in those predicted to respond (PPQ-positive, n = 40) but was 8 mo in those predicted not to respond (PPQ-negative, n = 27). The NETest result in responders was 67 ± 25 at baseline and significantly (P < 0.05) decreased (-37 ± 44%) at follow-up. The NETest result in nonresponders was 44 ± 23 at baseline and significantly (P < 0.05) increased (+76% ± 56%) at progression. Overall, the NETest changes (increases or decreases) were 90% accurate. Thirty patients underwent next-generation sequencing. Tumors were microsatellite-stable, and the median mutational burden was 1.8. Alterations involved mainly the mTOR/PTEN/TSC pathway (30%). No relationship was associated with PRRT response. Conclusion: Our interim analysis confirmed that PPQ is an accurate predictor of 177Lu-DOTATATE responsiveness (radiosensitivity) and that NETest changes accurately correlated with treatment response. Tissue-based molecular genetic information had little value in PRRT prediction. Blood-based gene signatures may improve the management of patients undergoing 177Lu-DOTATATE by providing information on tumor radiosensitivity and disease course, thus allowing individualized strategies. © 2023 by the Society of Nuclear Medicine and Molecular Imaging. |
| Keywords: | treatment outcome; aged; genetics; neuroendocrine tumor; genomics; octreotide; organometallic compound; organometallic compounds; somatostatin; neuroendocrine tumors; net; humans; human; male; female; prrt; netest; ppq; copper dotatate cu-64 |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 64 |
| Issue: | 4 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2023-04-01 |
| Start Page: | 567 |
| End Page: | 573 |
| Language: | English |
| DOI: | 10.2967/jnumed.122.264363 |
| PUBMED: | 36396457 |
| PROVIDER: | scopus |
| PMCID: | PMC10071782 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Lisa Bodei --Export Date: 1 May 2023 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work