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This chapter describes the possibility of using peptide receptor radionuclide therapy (PRRT) as neoadjuvant treatment. PRRT is acknowledged to be a palliative treatment. Recently it has been reported that tumor size decrease followed by surgical intervention might be achieved in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs labeled with beta emitters. Such outcome of therapy has been described in a relatively small group of patients. In those patients, the treatment enabled total or partial excision of the tumor, also with liver metastases. Reduction of tumor dimensions or total excision of the tumor corresponded with prolongation of overall survival. The discussed papers on this subject differ in details of treatment (utilization of various isotopes, total activity of the isotope, or combination with radiosensitizing chemotherapy). The chapter presents a brief review of recently published manuscripts.

Background: Somatostatin receptor scintigraphy (SRS) is a useful tool in the assessment of GEP-NET (gastroenteropancreatic neuroendocrine tumor) patients. The choice of appropriate settings of image reconstruction parameters is crucial in interpretation of these images. The aim of the study was to investigate how the GEP NET lesion signal to noise ratio (TCS/TCB) depends on different reconstruction settings for Flash 3D software (Siemens)., Methods: SRS results of 76 randomly selected patients with confirmed GEP-NET were analyzed. For SPECT studies the data were acquired using standard clinical settings 3-4 h after the injection of 740 MBq 99mTc-[EDDA/HYNIC] octreotate. To obtain final images the OSEM 3D Flash reconstruction with different settings and FBP reconstruction were used. First, the TCS/TCB ratio in voxels was analyzed for different combinations of the number of subsets and the number of iterations of the OSEM 3D Flash reconstruction. Secondly, the same ratio was analyzed for different parameters of the Gaussian filter (with FWHM = 2-4 times greater from the pixel size). Also the influence of scatter correction on the TCS/TCB ratio was investigated., Results: With increasing number of subsets and iterations, the increase of TCS/TCB ratio was observed. With increasing settings of Gauss [FWHM coefficient] filter, the decrease of TCS/TCB ratio was reported. The use of scatter correction slightly decreases the values of this ratio., Conclusions: OSEM algorithm provides a meaningfully better reconstruction of the SRS SPECT study as compared to the FBP technique. A high number of subsets improves image quality (images are smoother). Increasing number of iterations gives a better contrast and the shapes of lesions and organs are sharper. The choice of reconstruction parameters is a compromise between image qualitative appearance and its quantitative accuracy and should not be modified when comparing multiple studies of the same patient.

Material and Methods: Within the group of 47 patients treated with peptide receptor radionuclide therapy (PRRT), four patients were chosen: three with inoperable tumors without liver metastases and one with two lesions in the pancreas and metastases., Results: In all patients, after PRRT, the changes in the sum of the longest diameters of tumors were between -1% and -21%, resulting in stable disease reported [strict Response Evaluation Criteria in Solid Tumors (RECIST)]. But the measurements of tumor volume and attenuation in computed tomography and the tumor to nontumor ratio in somatostatin receptor scintigraphy resulted in different response assessments., Conclusions: The RECIST standard may be not sufficient to properly assess the therapy response in patients with neuroendocrine tumors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs., Material and Methods: Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed., Results: Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients)., Conclusions: The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET., Methods: Among 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST)., Results: The mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention., Conclusion: (1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.

Background: The aim of this study was to assess the efficacy and toxicity of peptide receptor radionuclide therapy (PRRT) with the use of the high affinity somatostatin receptor subtype 2 analogue, (90)Y labelled Tyr3-octreotate, ((90)Y-DOTATATE) in neuroendocrine tumours (NETs)., Material and Methods: 46 patients with disseminated or non-operable NET were enrolled in this study. The (90)Y-DOTATATE therapeutic activity was calculated per total body surface area up to a total of 7.4 GBq/m(2) administered in three to five cycles, repeated every four to nine weeks. Before and after the therapy, blood tests for haematology, kidney and liver function, and chromogranin A were performed., Results: Out of 46 (90)Y-DOTATATE treated patients, one died before completing the therapy and 16 died after completing the therapy, among them one due to myocardial infarction. After 12 month follow-up, stabilisation of disease was observed in 47%, partial remission in 31%, and progression in 9% of the 45 patients who completed the therapy. Five patients died before completion of 12 months of follow-up. One of the patients died due to myocardial infarction. In one case, the information after 12 months is incomplete. The progression free survival was 37.4 months. During 12 months follow-up, transient decrease of PLT, WBC and haemoglobin values was observed. A transient increase of creatinine level (within normal ranges) and decrease of GFR values were found., Conclusions: NETs (90)Y-DOTATATE therapy results in symptomatic relief and tumour mass reduction. The mild critical organ toxicity does not limit the PRRT of NETs.

Background: The aim of the study was to assess the effectiveness of peptide receptor radionuclide therapy (PRRT) in patients with non-functioning neuroendocrine pancreatic tumours (NFPNTs) and to compare survival rates in patients with NFPNTs and in patients with other neuroendocrine tumours (NETs) treated using radiolabelled somatostatin analogue in our Department. We would like to analyze factors potentially determining the effectiveness of the therapy and also to assess the myelo- and nephrotoxicity., Material and Methods: Fourteen patients with disseminated disease and/or inoperable NFPNT were qualified to PRRT based on positive SRS (somatostatin receptor scintigraphy). There were 5 men and 9 women, with Karnofsky's index>70%., Results: In the whole group of patients, partial response was observed in 21.4%, stabilization of the disease in 42.9%, and progression of the disease in 35.7% of patients. Mean observation time was 19±13 months, mean time to progression was 12±9 months, and mean time to death was 16±9 months. Six patients died--four of them due to progression of the disease, two due to myocardial infarction. After PRRT we did not observe clinically significant haemotoxicity and/or nephrotoxicity., Conclusions: 1. Peptide receptor radionuclide therapy may be a safe and effective treatment option in patients with NFPNTs, leading to stabilization or regression of the disease in the majority of patients. 2. There is no statistically significant difference in survival rate between patients with NFPNTs and NETs of other localization treated with PRRT.