***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND In the phase 3 RADIANT-4 trial , everolimus increased progression-free survival compared with placebo in patients with advanced , progressive , non-functional , well-differentiated gastrointestinal or lung neuroendocrine tumours ( NETs ) . We now report the health-related quality of life ( HRQOL ) secondary endpoint . METHODS RADIANT-4 is a multicentre , r and omised , double-blind , placebo-controlled , phase 3 trial done in 97 centres in 25 countries worldwide . Adults ( aged ≥18 years ) were eligible for the study if they had pathologically confirmed , advanced ( unresectable or metastatic ) , non-functional , well-differentiated ( grade 1 or 2 ) NETs of lung or gastrointestinal origin . Patients were r and omly allocated ( 2:1 ) using block r and omisation ( block size of three ) by an interactive voice response system to receive oral everolimus ( 10 mg per day ) or placebo , both with best supportive care , with stratification by tumour origin , WHO performance status , and previous somatostatin analogue treatment  . HRQOL was assessed with the Functional Assessment of Cancer Therapy-General ( FACT-G ) question naire at baseline ( visit 2 , day 1 ) , every 8 weeks ( ± 1 week ) during the study for the first 12 months after r and omisation , and every 12 weeks thereafter until study drug discontinuation . The primary endpoint , reported previously , was progression-free survival assessed by central review ; HRQOL was a prespecified secondary endpoint . The prespecified secondary outcome measure was time to definitive deterioration ( ≥7 points ) in FACT-G total score . Analyses were done on the full analysis set , consisting of all r and omised patients , by intention to treat . Only data obtained while receiving the r and omly allocated treatment were included in this analysis . Enrolment for RADIANT-4 was completed on Aug 23 , 2013 , but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , 302 patients were enrolled ; 205 were r and omly allocated everolimus and 97 were assigned placebo . At baseline , 193 ( 94 % ) of 205 patients assigned everolimus and 95 ( 98 % ) of 97 allocated placebo had completed either fully or partly the FACT-G question naire ; at week 48 , 70 ( 83 % ) of 84 patients assigned everolimus and 22 ( 85 % ) of 26 allocated placebo completed FACT-G. Median time to definitive deterioration in FACT-G total score was 11·27 months ( 95 % CI 9·27 - 19·35 ) with everolimus and 9·23 months ( 5·52-not estimable ) with placebo ( adjusted hazard ratio 0·81 , 95 % CI 0·55 - 1·21 ; log-rank p=0·31 ) . INTERPRETATION HRQOL was maintained for patients with advanced , non-functional , gastrointestinal or lung NETs , with no relevant differences noted between the everolimus and placebo groups . In view of the previous RADIANT-4 findings of longer progression-free survival  with everolimus , our findings suggest that everolimus delays disease progression while preserving overall HRQOL , even with the usual toxic effects related to active targeted drug treatment for cancer . FUNDING Novartis Pharmaceuticals Purpose Treatment options for neuroendocrine tumors ( NETs ) remain limited . This trial assessed the progression-free survival ( PFS ) of bevacizumab or interferon alfa-2b ( IFN-α-2b ) added to octreotide among patients with advanced NETs . Patients and Methods Southwest Oncology Group ( SWOG ) S0518 , a phase III study conducted in a US cooperative group system , enrolled patients with advanced grade s 1 and 2 NETs with progressive disease or other poor prognostic features . Patients were r and omly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week . The primary end point was central ly assessed PFS . This trial is registered with Clinical Trials.gov as NCT00569127 . Results A total of 427 patients was enrolled , of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b . The median PFS by central review was 16.6 months ( 95 % CI , 12.9 to 19.6 months ) in the bevacizumab arm and was 15.4 months ( 95 % CI , 9.6 to 18.6 months ) in the IFN arm ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.73 to 1.18 ; P = .55 ) . By site review , the median PFS times were 15.4 months ( 95 % CI , 12.6 to 17.2 months ) for bevacizumab and 10.6 months ( 95 % CI , 8.5 to 14.4 months ) for interferon ( HR , 0.90 ; 95 % CI , 0.72 to 1.12 ; P = .33 ) . Time to treatment failure was longer with bevacizumab than with IFN ( HR , 0.72 ; 95 % CI , 0.58 to 0.89 ; P = .003 ) . Confirmed radiologic response rates were 12 % ( 95 % CI , 8 % to 18 % ) for bevacizumab and 4 % ( 95 % CI , 2 % to 8 % ) for IFN  . Common adverse events with bevacizumab and octreotide  included hypertension ( 32 % ) , proteinuria ( 9 % ) , and fatigue ( 7 % ) ; with IFN and octreotide , they included fatigue ( 27 % ) , neutropenia ( 12 % ) , and nausea ( 6 % ) . Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms , which suggests that these agents have similar antitumor activity among patients with  advanced  NETs PURPOSE Effective systemic therapy for advanced carcinoid is lacking . The combination of bevacizumab ( BEV ) and pegylated ( PEG ) interferon alpha-2b was evaluated among patients with metastatic or unresectable carcinoid tumors . PATIENTS AND METHODS Forty-four patients on stable doses of octreotide  were r and omly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alpha-2b . At disease progression ( PD ) or at the end of 18 weeks ( whichever occurred earlier ) , patients received bevacizumab plus PEG interferon until progression . Functional computer tomography ( CT ) scans were performed to measure effect on tumor blood flow . RESULTS In the bevacizumab arm , four patients ( 18 % ) achieved confirmed partial response ( PR ) , 17 patients ( 77 % ) had stable disease ( SD ) , and one patient ( 5 % ) had PD . In the PEG interferon arm , 15 patients ( 68 % ) had SD and six patients ( 27 % ) had PD . Progression-free survival ( PFS ) rates after 18 weeks of monotherapy were 95 % in bevacizumab versus 68 % on the PEG interferon arm . The overall median PFS for all 44 patients is 63 weeks . Compared with paired baseline measurements on functional CT scans , we observed a 49 % ( P < .01 ) and 28 % ( P < .01 ) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab . No significant changes in tumor blood flow were observed following PEG interferon . PEG interferon alpha-2b treatment was associated with decrease in plasma basic fibroblast growth factor ( bFGF ; P = .04 ) and increase in plasma interleukin-18 ( IL-18 ; P < .01 ) . No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed . CONCLUSION Bevacizumab therapy result ed in objective responses , reduction of tumor blood flow , and longer PFS in patients with carcinoid than PEG interferon treatment These guidelines up date previous guidance published in 2005 . They have been revised by a group who are members of the UK and Irel and Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology , the Society for Endocrinology , the Association of Surgeons of Great Britain and Irel and ( and its Surgical Specialty Associations ) , the British Society of Gastrointestinal and Abdominal Radiology and others . The authors hip represents leaders of the various groups in the UK and Irel and Neuroendocrine Tumour Society , but a large amount of work has been carried out by other specialists , many of whom attended a guidelines conference in May 2009 . We have attempted to represent this work in the acknowledgements section . Over the past few years , there have been advances in the management of neuroendocrine tumours , which have included clearer characterisation , more specific and therapeutically relevant diagnosis , and improved treatments . However , there remain few r and omised trials in the field and the disease is uncommon , hence all evidence must be considered weak in comparison with other more common cancers . BACKGROUND The combination of streptozocin and fluorouracil has become the st and ard therapy for advanced islet-cell carcinoma . However , doxorubicin has also been shown to be active against this type of tumor , as has chlorozotocin , a drug that is structurally similar to streptozocin but less frequently causes vomiting . METHODS In this multicenter trial , we r and omly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens : streptozocin plus fluorouracil , streptozocin plus doxorubicin , or chlorozotocin alone .  The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens . RESULTS Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression , measured objective ly ( 69 percent vs. 45 percent , P = 0.05 ) , and the length of time to tumor progression ( median , 20 vs. 6.9 months ; P = 0.001 ) . Streptozocin plus doxorubicin also had a significant advantage in terms of survival ( median , 2.2 vs. 1.4 years ; P = 0.004 ) that was accentuated when we considered long-term survival ( greater than 2 years ) . Chlorozotocin alone produced a 30 percent regression rate , with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil . Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent , and the responses were transient . Toxic reactions to all regimens included vomiting , which was least severe with chlorozotocin ; hematologic depression ; and , with long-term therapy , renal insufficiency . CONCLUSIONS The combination of streptozocin and doxorubicin is superior to the current st and ard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma . Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil , but it produces fewer gastrointestinal side effects than the regimens containing streptozocin . It therefore merits study as a constituent of combination drug regimens BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of  
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Conclusions and Relevance The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs