Pulmonary neuroendocrine tumors (pNETs) account for 20-25% of all primary NETs. pNETs include low-grade typical carcinoid, intermediate-grade atypical carcinoids and high-grade malignancies (large cell neuroendocrine carcinoma and small cell lung cancer). Several therapeutic approaches are available for inoperable pNETs, but none of them has been definitely validated. Peptide receptor radionuclide therapy (PRRT) is an useful method for treatment of NETs; however, only few studies deal with PRRT in patients with pNETs.
The aim of this study is to evaluate efficacy and safety of PRRT in patients affected by pNETs.
We reviewed clinical records of 14 patients with pNET (7F and 7M; mean age, 65.7 years; range, 32-84) referred for PRRT. Six patients had low-grade pNET, six patients had intermediate-grade pNET and two patients had high-grade pNET. Ki-67 ranged from 2 to 80%. Diagnostic scintigraphy with 111In-Pentetreotide demonstrated lesional radiotracer uptake in all patients. Patients were treated with 111In-Pentetreotide (1-8 cycles; median, 3 cycles; median activity per cycle, 7 GBq; mean cumulative activity, 27.5 GBq) and/or 90Y-DOTATOC/DOTATATE (2-4 cycles; median, 3 cycles; median activity per cycle, 1.8 GBq; mean cumulative activity, 5.5 GBq) and/or 177Lu-DOTATATE (1-5 cycles; median, 2 cycles; median activity per cycle, 3.7 GBq; mean cumulative activity, 8.8 GBq). Each patient underwent 1 to 8 PRRT cycles. Intravenous aminoacids were administered to minimize renal damage. Eleven patients had comorbility factors (diabetes, hypertension, dyslipidemia, chronic obstructive pulmonary disease, renal failure). Objective efficacy of PRRT was evaluated according to RECIST criteria. Moreover, performance status (Karnofsky score) was evaluated before and after PRRT.
Objective response was: partial response in 3 (21.4%) cases, stable disease in 7 patients (50%), (overall disease control rate: 71.4%), and progressive disease in 4 patients (28.6%); namely, PR or SD was achieved by PRRT in 5/9 patients presenting with PD. No treated patient had acute toxicity. No short or long term renal function impairment was observed. Mild bone marrow toxicity (transient leucopenia and/or anemia and/or thrombocytopenia grade I WHO) was observed in 3 patients (21.4%). Comparing disease state at enrollement and after PRRT, a statistical significant difference was found (χ2=5.149; P=0.02).
Our study shows that PRRT should be considered in the management of pNETs, because of its safety and efficacy. The treatment results in disease control in about 71% of patients and systemic toxicity is limited and reversible.