W Willinek

Predictors of Long-Term Outcome in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate

Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival. Methods: We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with 177Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan–Meier curve method (log-rank test) and multivariate analysis (P < 0.05). Results: The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3–33.7) and 55 mo (95% confidence interval, 48.8–61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1–3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively. Conclusion: The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient’s performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2—in particular, between G1 (Ki-67 index of 1%–2%) and low-range G2 (Ki-67 index of 3%–10%)—provides prognostic stratification.

90Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy

Previous radiation therapy of the liver is a contraindication for performing 90Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated. Methods: We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with 90Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan–Meier method (log-rank test, P < 0.05). Results: The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18–58 mo). The mean previous cumulative activity of 177Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of 90Y microspheres was 3.4 ± 2.1 GBq, administered to the whole liver in a single session (n = 8 patients), in a sequential lobar fashion (n = 10 patients), or to only 1 liver lobe (n = 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4–54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47–61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P = 0.007). Conclusion: Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liver-dominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied 90Y activities and considerable previous cumulative activities of 177Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.

Is this really a true case of NSF following Gadovist exposure alone

and preserved renal function, and finally, G3 (severe) included the patients with sclerotic lesions in advanced chronic glomerulonephritis. The 20-year cumulative failure, estimated bymeans of Kaplan–Meier method, was observed in none of the patients with G1, in 35.6% with G2 and 92.9% of G3. On the basis of these data, we focused our attention to the patients with moderate lesions (G2) at renal biopsy who are potential progressors to ESKD. A randomized controlled trial including G1 (mild) and G3 (severe) IgAN patients would not have yielded any novel finding. The addition of corticosteroids makes sense only in IgAN patients with G2, proteinuria and preserved renal function, because they are at high risk to progress towards ESKD. On the other hand, we believe that ACE-I is sufficient in patients with minimal lesions and at low risk to progress towards ESKD and in patients with sclerotic lesions that cannot benefit from corticosteroids. In conclusion, our randomized controlled trial suggests to administer corticosteroids (6 months) and ACE-I in IgAN patients with moderate renal lesions (focal segmental or diffuse proliferative) and proteinuria >1.0 g/24 h. In our clinical practice, IgAN patients with mild or severe renal lesions receive only ACE-I.