Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine

Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Simon, Birgit; Mayer, Karin; Biersack, Hans‐Jürgen; Ezziddin, Samer

doi:10.1007/s00259-015-3041-6

Cited by 105 publications

(80 citation statements)

References 46 publications

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“…Our cohort consisted of a heterogenous population with a range of ages and primary tumour sites. For patients who met all protocol selection criteria, the estimated median OS of 50.7 months was consistent with OS rates from recent large ( n > 50) Australian and international studies . Characteristics associated with better survival were a low Ki‐67 proliferation index and GEP NET primary site.…”

Section: Discussionsupporting

confidence: 76%

Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

Lin

Chen

Little

et al. 2019

Internal Medicine Journal

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Background Peptide receptor radionuclide therapy with 177Lu‐DOTATATE is a promising treatment for inoperable or metastatic neuroendocrine tumours (NET). In 2015, the NSW Ministry of Health provided funding for 177Lu‐DOTATATE treatment of NET under an evaluation framework. Aims To examine the safety and outcomes of NET patients treated with 177Lu‐DOTATATE under the evaluation framework and assess the statewide implementation of the NSW Lutate therapy referral and protocol for neuroendocrine cancer patients. Methods A quality of care clinical audit was conducted on all NET patients treated with 177Lu‐DOTATATE from October 2010 to October 2015 at St George Hospital, and from August 2013 to March 2017 at Royal North Shore Hospital. Percentage of patients who met protocol selection criteria was calculated. Survival was estimated using the Kaplan–Meier method. Adjusted regression analyses assessed associations between key clinical factors and outcomes. Results A total of 279 patients was treated. Statewide protocol implementation led to an increase from 60.5 to 83.8% in patients meeting selection criteria. Estimated median overall survival was significantly longer for patients who met selection criteria compared with those who did not (50.7 vs 34.2 months) (P = 0.018). This was driven by the significantly worse overall survival in patients who failed exclusion criteria (P < 0.001). 177Lu‐DOTATATE was well tolerated with haematological, renal and hepatic treatment‐related serious adverse events experienced by 9.7, 0.4 and 0.4% of patients respectively. Conclusions 177Lu‐DOTATATE is a promising treatment for advanced NET. Superior survival in patients who met selection criteria emphasise the importance of protocol adherence.

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Section: Discussionsupporting

confidence: 76%

Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

Lin

Chen

Little

et al. 2019

Internal Medicine Journal

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“…For example, a 30% decrease in CgA (from pretreatment levels) is considered predictive of SSA efficacy [38], while an increase in three consecutive measurements is considered to anticipate relapse after midgut surgery [39]. Some authors proposed that alterations of ≥25% in CgA may have good sensitivities (>75%) and specificities (>85%) for predicting disease events [33] while others suggested that levels twice the ULN (∼300 µg/l or 300 ng/ml) [32] or higher (≥600) [40] are effective predictors of disease progression. Irrespective of the cutoff levels proposed, numerous technical issues, e.g.…”

Section: Discussionmentioning

confidence: 99%

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

et al. 2016

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Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes (>25%) in consistently predicting disease alterations (40%, p < 2 × 10^-5, χ² = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ² = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ² = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.

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“…These parameters makes Lutetium-177 the ideal radionuclide for PRRT. Treatment with beta-emitting radiolabeled somatostatin analogs results in impressive percentages of tumor regression (7)(8)(9)(10). Also, success monitored as time to progression (TTP), progression free survival (PFS) and overall survival (OS) has been reported in uncontrolled studies (8,11).…”

Section: Introductionmentioning

confidence: 98%

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors

Brabander

Zwan

Teunissen

et al. 2017

Clinical Cancer Research

473

383

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Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [Lu-DOTA,Tyr]octreotate (Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy. For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq)Lu-DOTATATE before 2013 was further analyzed for efficacy and survival. The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred. PRRT with Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT withLu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. .

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Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine

Cited by 105 publications

References 46 publications

Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors

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Specific efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours of the small intestine

Cited by 105 publications

References 46 publications

Safety and outcomes of 177Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

Safety and outcomes of 177Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors

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Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

Safety and outcomes of ¹⁷⁷Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia