Long-term outcome and toxicity after dose-intensified treatment with 131I-MIBG for advanced metastatic carcinoid tumors.

UNLABELLED: Reported experience with systemic (131)I-metaiodobenzylguanidine ((131)I-MIBG) therapy of neuroendocrine tumors comprises different dosing schemes. The aim of this study was to assess the long-term outcome and toxicity of treatment with 11.1 GBq (300 mCi) of (131)I-MIBG per cycle. METHODS: We performed a retrospective review of 31 patients with advanced metastatic neuroendocrine tumors (20 with carcinoid tumors and 11 with other tumors) treated with (131)I-MIBG. Treatment outcome was analyzed for patients with carcinoid tumors (the most common tumors in this study), and toxicity was analyzed for the entire patient cohort (n = 31). Treatment comprised 11.1 GBq (300 mCi) per course and minimum intervals of 3 mo. The radiographic response was classified according to modified Response Evaluation Criteria in Solid Tumors. Toxicity was determined according to Common Terminology Criteria for Adverse Events (version 3.0) for all laboratory data at regular follow-up visits and during outpatient care, including complete blood counts and hepatic and renal function tests. Survival analysis was performed with the Kaplan-Meier curve method (log rank test; P < 0.05). RESULTS: The radiographic responses in patients with carcinoid tumors comprised a minor response in 2 patients (10%), stable disease in 16 patients (80%; median time to progression, 34 mo), and progressive disease in 2 patients (10%). The symptomatic responses in patients with functioning carcinoid tumors comprised complete resolution in 3 of the 11 evaluable symptomatic patients (27%), partial resolution in 6 patients (55%), and no significant change in 11 patients. The median overall survival in patients with carcinoid tumors was 47 mo (95% confidence interval, 32-62), and the median progression-free survival was 34 mo (95% confidence interval, 13-55). Relevant treatment toxicities were confined to transient myelosuppression of grade 3 or 4 in 15.3% (leukopenia) and 7.6% (thrombocytopenia) of applied cycles and a suspected late adverse event (3% of patients), myelodysplastic syndrome, after a cumulative administered activity of 66.6 GBq. The most frequent nonhematologic side effect was mild nausea (grade 1 or 2), which was observed in 28% of administered cycles. No hepatic or renal toxicities were noted. CONCLUSION: Dose-intensified treatment with (131)I-MIBG at a fixed dose of 11.1 GBq (300 mCi) per cycle is safe and offers effective palliation of symptoms and disease stabilization in patients with advanced carcinoid tumors. The favorable survival and limited toxicity suggest that high cycle activities are suitable and that this modality may be used for targeted carcinoid treatment--either as an alternative or as an adjunct to other existing therapeutic options.

Hepatic volume changes induced by radioembolization with 90Y resin microspheres. A single-centre study.

PURPOSE: Lobar radioembolization (RE) of the liver can result in reduction in volume of the ipsilateral lobe as well as hypertrophy of the contralateral lobe. Theoretically, hypertrophy of the contralateral liver lobe after RE could increase the chance of a successful liver resection, especially in patients with limited liver function reserve. The aim of this preliminary study was to evaluate the early effects of RE with resin microspheres on the volumes of the liver lobes and spleen. METHODS: We retrospectively investigated 24 patients (12 women, 44-78 years old) with different types of cancer and liver-dominant metastatic disease who had undergone RE of the liver with resin microspheres. Changes in the volumes of the liver lobes and spleen were quantified by CT before and about 4 to 8 weeks after treatment. RESULTS: Of the 24 patients, 17 suffered from metastases in both liver lobes (group A) and 7 had metastases only in the right liver lobe (group B). The patients in the group A underwent sequential treatment starting with the right liver lobe. The median administered dose was 1.75 GBq. RE was associated with a median increase in volume of the left liver lobe of 34 % (P < 0.001) and a median decrease in volume of the right liver lobe of 11 % (P = 0.03). The volume of the spleen showed a median increase of 17 % (P = 0.01). Separate analysis of the two groups showed a median increases in volume of the left liver lobe of 30 % (P = 0.001) in group A and 70 % (P = 0.01) in group B. There was no correlation between the injected dose and the volume alteration (r = 0.1-0.3). CONCLUSION: RE of the right liver lobe with resin microspheres caused a significant increase in the volume of the left liver lobe. This may allow liver resection in patients with metastases in the right liver lobe and a small left liver lobe.

Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors.

UNLABELLED: Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification. METHODS: Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P < 0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (>80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.

The role of combined imaging in metastatic medullary thyroid carcinoma: 111In-DTPA-octreotide and 131I/123I-MIBG as predictors for radionuclide therapy.

PURPOSE: The medical treatment of metastatic medullary thyroid carcinoma (MTC) is still questionable. The aim of this study was to evaluate a combined imaging protocol using 111In-DTPA-octreotide and 131I/123I-MIBG to decide whether targeted radiotherapy would be useful, and which radiopharmaceutical (90Y-DOTATOC or 131I-MIBG) would be more effective. METHODS: Eight patients (four men, four women; mean age 61 years) with metastatic MTC were included. Treatments were performed with 3,330 MBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of 3 months. RESULTS: The imaging procedure was positive in all eight patients: 111In-DTPA-octreotide imaging in five patients, 131I/123I-MIBG imaging in four patients. With respect to the number of metastatic lesions, MIBG imaging was less effective than octreotide. According to the results of combined imaging, we identified one patient to be treated with 90Y-DOTATOC, and three patients with 131I-MIBG. An overall antitumor effect was observed in all four patients, one with partial remission and three with stable disease. No relevant toxicity was observed. CONCLUSIONS: The combined imaging can increase the detection rate of metastatic foci in patients with MTC and identify more patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.