Dataset Information

Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

ABSTRACT: Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP-NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3-4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-? plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one ¹⁷⁷Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. ¹⁷⁷Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-? plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-? plus SSA (52.4%), ¹⁷⁷Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with ¹⁷⁷Lu-Dotatate.

SUBMITTER: Ricci C

PROVIDER: S-EPMC7835931 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

Ricci Claudio C Lamberti Giuseppe G Ingaldi Carlo C Mosconi Cristina C Pagano Nico N Alberici Laura L Ambrosini Valentina V Manuzzi Lisa L Monari Fabio F Malvi Deborah D Rosini Francesca F Minni Francesco F Campana Davide D Casadei Riccardo R

Cancers 20210119 2

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP-NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The p ...[more]

PMID: 33561087

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Project description:BackgroundSeveral risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.Patients and methodsA retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.ResultsTwo hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.ConclusionIn stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.

Project description:Microenvironment-related immune and inflammatory markers, when combined with established Ki-67 and morphology parameters, can improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Therefore, we evaluated the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP-NENs. For this purpose, formalin-fixed paraffin-embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN-, and fibroblast-related markers. A total of 314 patients were used to generate overall survival (OS) and disease-free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5-year OS and DFS. A total of 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 versus G3 GEP-NENs showed phenotypic divergence with immune-inflammatory markers. HLA, CD3, CD8, and PD-1/PD-L1 IHC expression separated G3 into two sub-categories with high versus low adaptive immunity-related features. MoTIFs PI for OS based on COX-2Tumor(T) > 4, PD-1Stromal(S) > 0, CD8S < 1, and HLA-IS < 1 was associated with worst survival (hazard ratio [HR] 2.50; 95% confidence interval [CI], 2.12-2.96; p < 0.0001). MoTIFs PI for DFS was based on COX-2T > 4, PD-1S > 4, HLA-IS < 1, HLA-IT < 2, HLA-DRS < 6 (HR 1.77; 95% CI, 1.58-1.99; p < 0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30-10.15; p < 0.001) and Ki-67 (HR 11.32; 95% CI, 5.28-24.24; p < 0.001) for OS, and morphology (PI = 0: HR 10.23; 95% CI, 5.67-18.47; PI = 5: HR 2.87; 95% CI, 1.21-6.81; p < 0.001) and MoTIFs PI for DFS in well-differentiated GEP-NENs (HR 6.21; 95% CI, 2.52-13.31; p < 0.001). We conclude that G1/G2 to G3 transition is associated with immune-inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki-67 improve 5-year DFS prediction in GEP-NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints.

Dataset Information

Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

Publications

Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

Similar Datasets

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