Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms

Abstract

Background: Neuroendocrine neoplasms are a group of tumors deriving from neural crest. They can be located in every tissue, but most commonly in gastrointestinal tract. Targeted therapy with use of radionuclides is an available and acceptable way of treatment, but its long-term safety is still to be determined, especially with sensitive methods. Methods: Study was performed on a group of 42 patients. They underwent full cycle (4 courses; 8–12 weekly intervals) of radioligand therapy with [177Lu]Lu-DOTATATE alone or tandem therapy with [177Lu]Lu-DOTATATE+[90Y]Y-DOTATATE. Late and long-term marrow and renal complications were assessed. Analysis focused on comparing data before first, fourth, and one year after the last course of RLT. Results: Study showed decreasing of all blood parameters in long-term observation, especially in lymphocytes line. Type of radioisotope, other diseases, primary tumor location, BMI, gender or age did not affect results. The only factor that had influence on hemoglobin and erythrocytes was decreased renal filtration. In long-term observation almost 10% decrease of renal filtration was observed. Type of isotope, gender, age, BMI did not affect these results. Moreover, reduction of urine IL-18, KIM-1, and albumin concentration has been observed. Conclusions: Though low-grade complications of radioligand therapy are possible, it stay a safe method of NEN treatment where benefits outweigh the risk.

Re-treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE of patients with progressive neuroendocrine neoplasm

“…The decrease of glomerular filtration rate and increase of creatinine serum concentration observed in the present study among patients undergoing radioligand therapy is consistent with the known negative impact of the treatment, but it can also be related to the natural decline in GFR values with age, estimated at approximately 1% in the Central European population [31][32][33]. The authors' prospective study published in 2023 showed a sustained decrease of GFR of about 10% one year after radioligand therapy of NEN patients [34]. Given that the kidneys are the critical organ for radioligand therapy, the greatest concerns and limitations of this treatment arise from the potential injury of the kidneys and permanent reduction in glomerular filtration [35].…”

“…Risk factors for bone marrow injury included age > 70 years, impaired kidney function, pre-existing cytopenia, and previous chemotherapy or radiotherapy [37]. The authors' previous study also confirmed that bone marrow function after the RLT was significantly disturbed [34,38]. During RLT a decrease in each bone marrow cell line was observed, however, statistically significant results regarded only leukocytes and lymphocytes.…”

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center

“…There is a lack of high-quality double-blind studies comparing monotherapy with [ 177 Lu]Lu-DOTA-TATE with tandem [ 177 Lu]Lu-DOTA-TATE/[ 90 Y]Y-DOTA-TATE, but physical features of 90 Y cause more concerns in using this type of treatment. A possible higher number of adverse events, like decreasing GFR, liver injury, or bone marrow dysfunction, was not statistically proven, with even some data advocating for higher effectiveness of the method in treating large tumors or metastases [13,15,[66][67][68].…”

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade

“…The results of the study group were similar to ones observed in previous studies. Despite reaching statistical significancy, the changes in described parameters were not clinically significant [ 42 , 43 ].…”