The Tyr Phenomenon: A Hypocalcemic Response in High-Volume Treatment Responders to 177Lu-Prostate-Specific Membrane Antigen Therapy.

177Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer. Rarer treatment-related adverse events have not yet been described. Methods: We present case reviews of 2 men with a marked hypocalcemic osteosclerotic response to 177Lu-PSMA-I&T therapy. A clinical dataset of 177Lu-PSMA-I&T therapy was evaluated to estimate the incidence and clinical association with hypocalcemia. Results: Forty-one of the 127 men (32%) had a serum calcium drop, and 6 (5%) developed clinical hypocalcemia during 177Lu-PSMA therapy. The baseline total tumor volume was significantly higher in those who developed hypocalcemia (median, 3,249 cm3 [interquartile range, 1,856-3,852] vs. 465 [interquartile range 135-1,172]; P = 0.002). The mean prostate-specific antigen response in those with hypocalcemia was 78% (SD, 24%). Conclusion: Hypocalcemia may occur in response to 177Lu-PSMA-I&T, particularly with both high-volume bone metastases and a significant prostate-specific antigen response, and may be severe, requiring corticosteroids. Further evaluation of 177Lu-PSMA-induced hypocalcemia is required to better understand mechanisms, optimal treatments, and repercussions from any subsequent osteosclerotic response.

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS).

PURPOSE: 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate. METHODS: A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals). RESULTS: Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively. CONCLUSION: High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.