Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr2) in neuroendocrine tumors (NETs).

Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor.

This book is a timely textbook that covers all aspects of neuroendocrine tumors (NET) from epidemiology, pathological classification and evaluation and molecular biology through to diagnostic imaging

UNLABELLED:Meningiomas express members of the somatostatin receptor family. The present study assessed the long-term benefits and harm of somatostatin-based radiopeptide therapy in meningioma patients. METHODS:Patients with progressive unresectable meningioma were treated with (90)Y-DOTATOC and (177)Lu-DOTATOC until tumor progression or permanent toxicity occurred. Multivariable Cox regression analyses were used to study predictors of survival. RESULTS:Overall, 74 treatment cycles were performed on 34 patients. Stable disease was achieved in 23 patients. Severe hematotoxicity occurred in 3 patients, and severe renal toxicity in 1 patient. Mean survival was 8.6 y from the time of recruitment. Stable disease after treatment (hazard ratio, 0.017 vs. progressive disease; 95% confidence interval, 0.001-0.35; n = 34; P = 0.01) and high tumor uptake (hazard ratio, 0.046 vs. intermediate or low tumor uptake; 95% confidence interval, 0.004-0.63; n = 34; P = 0.019) were associated with longer survival. CONCLUSION:(90)Y-DOTATOC and (177)Lu-DOTATOC are promising tools for treating progressive unresectable meningioma, especially in cases of high tracer uptake in the tumor.

We aimed to explore the effects of (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC on survival of patients with metastasized gastrinoma. Patients with progressive metastasized gastrinoma were treated with repeated cycles of (90)Y-DOTATOC or with cycles alternating between (90)Y-DOTATOC and (177)Lu-DOTATOC until tumor progression or permanent toxicity. Multivariable Cox regression analyses were used to study predictors of survival. A total of 36 patients were enrolled; 30 patients received (90)Y-DOTATOC (median activity per patient 11.8GBq; range: 6.1-62.2GBq) and 6 patients received (90)Y-DOTATOC plus (177)Lu-DOTATOC (median activity per patient: 14.8GBq; range: 7.4-14.8GBq). Response was found in 26 patients (72.2%), including morphological (n=12, 33.3%), biochemical (n=14, 38.9%) and/or clinical response (n=6, 16.2%). A total of 21 patients (58.3%) experienced hematotoxicity grade 1/2, while 1 patient (2.8%) experienced hematotoxicity grade 3; no grade 4 hematotoxicity occurred. Furthermore, 2 patients (5.6%) developed grade 4 renal toxicity; no grade 5 renal toxicity occurred. Responders had a significantly longer median survival from time of enrollment than non-responders (45.1 months, range: 37.1-53.1 months vs. 12.6 months, range: 11.0-14.2, hazard ratio: 0.12 (0.027-0.52), p=0.005). Additionally, there was a trend towards longer median survival with (90)Y-DOTATOC plus (177)Lu-DOTATOC as compared to (90)Y-DOTATOC alone (60.2 months, range: 19.8-100.6 months vs. 27.0 months, range: 4.0-50.0, hazard ratio: 0.21 (0.01-3.98), p=0.16). Response to (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC therapy is associated with a longer survival in patients with metastasized gastrinoma. Both treatment regimens are promising tools for management of progressive gastrinoma.

A 46-year-old female presented initially with severe back pain and left-sided radicular symptoms. A magnetic resonance image of the spine was performed because of a suspected discal hernia at level L5/S1. It showed the incidental finding of a large tumor of 12 × 6.5 × 11 cm suspected to originate from the retroperitoneum on the right side. A staging computed tomography 2 days later showed no evidence of local or distant metastases but revealed suspected contact of the tumor with the duodenum, the ascending colon, and the inferior vena cava (Fig 1). Laboratory results were unremarkable. Family history was negative for malignancies. Personal history revealed solely a series of suspected abdominal traumata during childhood and adolescence due to intensive gymnastics on a professional level.

Objective: We aim to emphasize crucial differences between osteosarcomas of the jaws (OSj) and those of the peripheral skeleton (OSp) and to question current therapeutic concepts in presenting a comprehensive study on 214 patients.Background: OSj account for only 6% of all osteosarcomas (OS) but seem to represent a clinically and prognostically distinct subgroup. Due to the limited experience with this rare disease it is still a matter of debate if (neo-) adjuvant chemotherapy can improve the outcome of patients like in OSp or if OSj patients can be cured by surgical treatment only.Methods: 214 well characterized OSj patients with long-term follow up are presented and the influence of clinico-pathological parameters affecting the prognosis of patients is discussed.Results: The OSj patients in our series showed metastatic spread far less frequently (17.6% of cases) and later in the course of the disease (26 months after diagnosis on average) compared to OSp. Consequently, complete resection of the tumors resulted in an excellent long-term survival (83.2% after 10 years). Neoadjuvant or adjuvant treatment applied in a smaller subset of patients, furthermore, failed to show any additional favorable effect.Conclusion: Whereas OSp is regarded as systemic disease at the time of diagnosis in which > 90% of patients develop lung metastases without multimodality treatment, the vast majority of OSj patients seem to be curable by complete resection only. Based on the findings presented here, multimodality treatment should be critically scrutinized in OSj patients. (C) 2013 Elsevier Ltd. All rights reserved.

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [ 90 Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [ 90 Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [ 90 Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [ 90 Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [ 90 Y-DOTA]-TOC could facilitate tailoring [ 90 Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [ 90 Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number: NCT00978211

PURPOSE:Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.PATIENTS AND METHODS:In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles.RESULTS:A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups.CONCLUSION:[(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

PURPOSETo investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers.PATIENTS AND METHODSIn a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity.RESULTSOverall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P < .001), biochemical (HR, 0.75; 95% CI, 0.59 to 0.96; 35.3 v 25.7 months; P = .023), and clinical response (HR, 0.68; 95% CI, 0.56 to 0.82; 36.8 v 23.5 months; P < .001). Overall, 142 patients (12.8%) developed grade 3 to 4 transient hematologic toxicities, and 103 patients (9.2%) experienced grade 4 to 5 permanent renal toxicity. Multivariable regression revealed that tumoral uptake in the initial imaging study was predictive for overall survival (HR, 0.45; 95% CI, 0.29 to 0.69; P < .001), whereas the initial kidney uptake was predictive for severe renal toxicity (HR, 1.59; 95% CI, 1.17 to 2.17; P = .003).CONCLUSIONThis study documents the long-term outcome of [(90)Y-DOTA]-TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.