***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: As incidence data on gastroenteropancreatic neuroendocrine tumours ( GEP-NETs ) have so far only been retrospectively obtained and based on inhomogeneous material , we conducted a prospect i ve study in Austria collecting all newly diagnosed GEP-NETs during 1 year . Using the current WHO classification , the tumor , nodes , metastases ( TNM ) staging and Ki67 grading and the st and ard diagnostic procedure proposed by the European Neuroendocrine Tumor Society ( ENETS ) , GEP-NETs from 285 patients ( male : 148 ; female : 137 ) were recorded . The annual incidence rates were 2.51 per 100,000 inhabitants for men , 2.36 per 100,000 for women . The stomach ( 23 % ) was the main site , followed by appendix ( 21 % ) , small intestine ( 15 % ) and rectum ( 14 % ) . Patients with appendiceal tumours were significantly younger than patients with tumours in any other site . About 46.0 % were classified as benign , 15.4 % as uncertain , 31.9 % as well differentiated malignant and 6.7 % as poorly differentiated malignant . Patients with benign or uncertain tumours were significantly younger than patients with malignant tumours . Among the malignant tumours of the digestive tract , 1.49 % arose from neuroendocrine cells . For malignant gastrointestinal NETs , the incidence was 0.80 per 100,000 : 40.9 % were ENETS stage I , 23.8 % stage II , 11.6 % stage III and 23.8 % stage IV . The majority ( 59.7 % ) were grade 1 , 31.2 % grade 2 and 9.1 % grade 3 . NETs of the digestive tract are more common than previously reported ; the majority show benign behaviour , are located in the stomach and are well differentiated . G3 tumours are very rare Abstract . The aim of this study was to determine the maximum tolerated dose of 90Y-DOTATOC per cycle administered in association with amino acid solution as kidney protection in patients with somatostatin receptor-positive tumours . Forty patients in eight groups received two cycles of 90Y-DOTATOC , with activity increased by 0.37 GBq per group , starting at 2.96 and terminating at 5.55 GBq . All patients received lysine ± arginine infusion immediately before and after therapy . Forty-eight percent developed acute grade I – II gastrointestinal toxicity ( nausea and vomiting ) after amino acid infusion whereas no acute adverse reactions occurred after 90Y-DOTATOC injection up to 5.55 GBq/cycle . Grade III haematological toxicity occurred in three of seven ( 43 % ) patients receiving 5.18 GBq , which was defined as the maximum tolerable activity per cycle . Objective therapeutic responses occurred . Five GBq per cycle is the recommended dosage of 90Y-DOTATOC when amino acids are given to protect the kidneys . Although no patients developed acute kidney toxicity , delayed kidney toxicity remains a major concern , limiting the cumulative dose to ~25 Gy . The way forward with this treatment would seem to be to identify more effective renal protective agents , in order to be able to increase the cumulative injectable activity and hence tumour dose In the CLARINET study , lanreotide Autogel ( depot in USA ) significantly prolonged progression-free survival ( PFS ) in patients with metastatic pancreatic/intestinal neuroendocrine tumours ( NETs ) . We report long-term safety and additional efficacy data from the open-label extension ( OLE ) . Patients with metastatic grade 1/2 ( Ki-67 ≤10 % ) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg ( n=101 ) or placebo ( n=103 ) for 96 weeks or until death/progressive disease ( PD ) in CLARINET study . Patients with stable disease ( SD ) at core study end ( lanreotide/placebo ) or PD ( placebo only ) continued or switched to lanreotide in the OLE . In total , 88 patients ( previously : lanreotide , n=41 ; placebo , n=47 ) participated : 38 % had pancreatic , 39 % midgut and 23 % other/unknown primary tumours . Patients continuing lanreotide reported fewer adverse events ( AEs ) ( all and treatment-related ) during OLE than core study . Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies , except more diarrhoea was considered treatment-related in OLE ( overall diarrhoea unchanged ) . Median lanreotide PFS ( core study r and omisation to PD in core/OLE ; n=101 ) was 32.8 months ( 95 % CI : 30.9 , 68.0 ) . A sensitivity analysis , addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE ( n=13 ) had PD 24 weeks after last core assessment , found median PFS remaining consistent : 30.8 months ( 95 % CI : 30.0 , 31.3 ) . Median time to further PD  after placebo-to-lanreotide switch ( n=32 ) was 14.0 months ( 10.1 ; not reached ) . This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability . CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs Somatostatin analogues ( SSA ) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors ( NET ) . A post hoc analysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 ( RADIANT-2 ) study was conducted to assess the efficacy of octreotide long-acting repeatable ( LAR ) on progression-free survival ( PFS ) and overall survival ( OS ) estimated using the Kaplan – Meier method . Out of 213 patients r and omized to placebo plus octreotide LAR in RADIANT-2 , 196 patients with foregut , midgut , or hindgut NET were considered for present analysis . Of these , 41 patients were SSA-treatment naïve and 155 had received SSA therapy before study entry . For SSA-naïve patients , median PFS by adjudicated central review was 13.6 ( 95 % CI 8.2–22.7 ) months . For SSA-naïve patients with midgut NET ( n=24 ) , median PFS was 22.2 ( 95 % CI 8.3–29.5 ) months . For patients who had received SSA previously , the median PFS was 11.1 ( 95 % CI 8.4–14.3 ) months . Among the SSA-pretreated  patients who had midgut NET ( n=119 ) , the median PFS was 12.0 ( 95 % CI 8.4–19.3 ) months . Median OS was 35.8 ( 95 % CI 32.5–48.9 ) months for patients in the placebo plus octreotide LAR arm ; 50.6 ( 36.4 – not reached ) months for SSA-naïve patients and 33.5 ( 95 % CI 27.5–44.7 ) months for those who had received prior SSA . This post hoc analysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy About 40 % of nonfunctioning pancreatic endocrine carcinomas ( NF-PEC ) can not be cured by surgery due to advanced stage disease . Somatostatin analogues have been proposed as first line therapy in these cases . We performed a prospect i ve phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy . Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m . at diagnosis . The immunohistochemical expression of somatostatin receptor 2 ( SSTR2 ) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours . The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67 . Eight patients ( 38 % ) had stable disease ( SD ) after a median follow-up of 49.5 months . Thirteen patients ( 62 % ) developed progression after a median of 18 months . Tumour progression correlated with a proliferative index > or=5 % ( P=0.016 ) , weight loss ( P=0.006 ) and absence of abdominal pain ( P=0.003 ) at diagnosis . Other clinical ( age , gender and primary tumour resection ) or pathological parameters ( site , size and liver metastasis ) lacked significant correlation with tumour progression . No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable ( n=5 ) and seven tumours that progressed ( n=7 ) . Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38 % of patients . A Ki-67 index > or=5 % and /or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease PURPOSE Despite the fact that most gastroenteropancreatic neuroendocrine tumors ( GEPNETs ) are slow-growing , median overall survival ( OS ) in patients with liver metastases is 2 to 4 years . In metastatic disease , cytoreductive therapeutic options are limited . A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate . Here we report on the toxicity and efficacy of this treatment , performed in over 500 patients . PATIENTS AND METHODS Patients were treated up to a cumulative dose of 750 to 800 mCi ( 27.8 - 29.6 GBq ) , usually in four treatment cycles , with treatment intervals of 6 to 10 weeks .  Toxicity analysis was done in 504 patients , and efficacy analysis in 310 patients . RESULTS Any hematologic toxicity grade 3 or 4 occurred after 3.6 % of administrations . Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients , and temporary , nonfatal , liver toxicity in two patients . Complete and partial tumor remissions occurred in 2 % and 28 % of 310 GEPNET patients , respectively . Minor tumor response ( decrease in size > 25 % and < 50 % ) occurred in 16 % . Median time to progression was 40 months . Median OS from start of treatment was 46 months , median OS from diagnosis was 128 months . Compared with historical controls , there was a survival benefit of 40 to 72 months from diagnosis . CONCLUSION Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects . Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities . Compared with historical controls , there is a benefit in OS from time of diagnosis of several years BACKGROUND & AIMS The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure ( progression , death , stop of study treatment ) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut ( mainly pancreatic ) and midgut tumors . METHODS One hundred nine of 125 registered patients were r and omized starting in January 1995 , and 105 patients ( 51 monotherapy , 54 combination treatment ) were finally analyzed in March 2000 .  Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging .  Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not r and omized because of stable disease . RESULTS Partial tumor regression occurred in 2.9 % , 1.9 % , and 5.7 % and stabilization of tumor growth in 44.8 % , 27.6 % , and 15.2 % at 3 , 6 , and 12 months , respectively , with no significant differences between both treatment arms . In March 2000 , 9.5 % of patients were in treatment . Time to treatment failure and long-term survival did not differ significantly between the 2 groups , with a median survival of 32 and 54 months for the octreotide and the combination groups , respectively . Survival was longer in patients not r and omized because of stable disease ( median , 68 months ) and in those with low nuclear Ki-67 . A trend toward longer survival was shown for patients with slow spontaneous tumor growth before r and omization . Patients responding to treatment lived longer than unresponsive patients . CONCLUSIONS Combination treatment was not superior to monotherapy concerning progression-free and long-term survival . Patients responding to treatment and those with 
    Output:
    
In conclusion , SSAs showed an antiproliferative effect in advanced GEP-NETs , with a good safety profile