272 research outputs found
Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment
Purpose: To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment.Materials and Methods: This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was mea-sured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test.Results: The study included 119 patients (mean age, 60 years +/- 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in re-sponders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion: Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treat-ments, with better discrimination than RECIST and mRECIST
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11
Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors
Background: Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged progression-free survival (PFS) versus placebo.
Methods: During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors [RECIST] v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR0); 12-24 weeks before randomization versus baseline; each treatment visit versus baseline (TGRTx-0); between consecutive treatment visits (TGRTx-Tx). To assess TGR as a measure of prognosis, PFS was compared for TGR0 subgroups stratified by optimum TGR0 cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS.
Results: TGR0 revealed tumors growing during pre-treatment (median [interquartile range] TGR0: lanreotide 2.1%/month [0.2; 6.1]; placebo 2.7%/month [0.15; 6.8]), contrary to RECIST status. TGR was significantly reduced by 12 weeks with lanreotide versus placebo (difference in least-square mean TGR0-12 of - 2.9 [- 5.1, - 0.8], p = 0.008), a difference that was maintained at most subsequent visits. TGR0 > 4%/month had greater risk of progression/death than β€4%/month (hazard ratio 4.1; [95% CI 2.5-6.5]; p < 0.001); multivariate analysis revealed lanreotide treatment, progression at baseline, TGR0, hepatic tumor load, and primary tumor type were independently associated with PFS.
Conclusions: TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity.
Trial registration: Retrospective registration, 18 July 2006; EudraCT: 2005-004904-35; ClinicalTrials.gov: NCT00353496
Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: The CLARINET open-label extension study
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 %) nonfunctioning 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 randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection
Π Π΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ ΠΏΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠΈΠΌ ΠΈΠ»ΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠ΅ΠΉ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ±Π° ΠΈ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠ°
.ΠΠ° ΡΠ΅Π³ΠΎΠ΄Π½ΡΡΠ½ΠΈΠΉ Π΄Π΅Π½Ρ ΡΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ 2-ΠΉ Π»ΠΈΠ½ΠΈΠΈ Π΄Π»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ ΠΏΠΎΡΠ»Π΅ Π½Π΅ΡΠ΄Π°ΡΠΈ 1-ΠΉ Π»ΠΈΠ½ΠΈΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·. ΠΠ΅Π΄Π°Π²Π½ΠΎ Π±ΡΠ»ΠΈ ΠΎΠ΄ΠΎΠ±ΡΠ΅Π½Ρ Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΊΠ°Π±ΠΎΠ·Π°Π½ΡΠΈΠ½ΠΈΠ±, Π½ΠΈΠ²ΠΎΠ»ΡΠΌΠ°Π± ΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΡ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ± + ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡ. ΠΡΡΡΡΡΡΠ²ΠΈΠ΅ Π½Π°Π΄Π΅ΠΆΠ½ΡΡ
Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ², Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½Π½ΠΎΡΡΡ Π΄Π°Π½Π½ΡΡ
ΠΏΡΠΎΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΉ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π·Π°ΡΡΡΠ΄Π½ΡΡΡ Π²ΡΠ±ΠΎΡ ΡΠ°ΠΊΡΠΈΠΊΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ 2-ΠΉ Π»ΠΈΠ½ΠΈΠΈ Π² ΡΡΡΠΈΠ½Π½ΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅.Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌ ΠΎΠ±Π·ΠΎΡΠ΅ ΠΌΡ ΠΎΠΏΠΈΡΡΠ²Π°Π΅ΠΌ ΠΏΡΠΎΡΠΈΠ»Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ± + ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡ ΠΏΡΠΈ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΌ ΡΠ°ΠΊΠ΅. ΠΠ°Π½Π½Π°Ρ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΡ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ»Π° Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΠΎΠ±ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° Π½Π° ΡΠ΅ΡΠ°ΠΏΠΈΡ, Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ Π±Π΅Π· ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΡ
Ρ ΠΏΠ΅ΡΠ΅ΠΊΡΠ΅ΡΡΠ½ΡΠΌ Π΄ΠΈΠ·Π°ΠΉΠ½ΠΎΠΌ. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ ΠΏΡΠΎΡΠΈΠ»Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΡΡΠΎΠΉ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ, Π²ΠΊΠ»ΡΡΠ°Ρ ΡΠ°ΡΡΠΎΡΡ ΠΎΠ±ΡΠΈΡ
ΠΈ ΡΡΠΆΠ΅Π»ΡΡ
Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ²Π»Π΅Π½ΠΈΠΉ, ΠΏΡΠΎΡΠ΅Π½Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠΌ ΠΏΠΎΡΡΠ΅Π±ΠΎΠ²Π°Π»ΠΎΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ Π΄ΠΎΠ·Ρ ΠΈΠ»ΠΈ ΠΏΠΎΠ»Π½Π°Ρ ΠΎΡΠΌΠ΅Π½Π° Π»Π΅ΡΠ΅Π½ΠΈΡ, Π±ΡΠ» ΠΌΠ΅Π½Π΅Π΅ Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΌ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π΄ΠΎΡΡΡΠΏΠ½ΡΠΌΠΈ Π²Π°ΡΠΈΠ°Π½ΡΠ°ΠΌΠΈ ΠΌΠΎΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ. ΠΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ Π±ΠΎΠ»Π΅Π΅ ΡΡΠ°ΡΠ΅Π»ΡΠ½ΡΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ ΠΌΠΎΠΆΠ΅Ρ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°ΡΡ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠΈΡ
Π΄Π²ΡΡ
ΡΡΠ΅Π΄ΡΡΠ², ΠΎΠ΄Π½ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ Π·Π°ΡΠΈΡΠ°Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡ Π½Π΅ΠΎΠΏΡΠ°Π²Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π²ΡΠ΅Π΄Π°.Π¦Π΅Π»Ρ β ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΌΠ΅ΠΆΠ΄ΠΈΡΡΠΈΠΏΠ»ΠΈΠ½Π°ΡΠ½ΡΡ
ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ Π΄Π»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈ Π»ΠΈΡ, ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΡΡΠΈΡ
ΡΡ
ΠΎΠ΄ Π·Π° Π½ΠΈΠΌΠΈ, ΠΏΠ΅ΡΠ΅Π΄ Π½Π°ΡΠ°Π»ΠΎΠΌ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠ΅ΠΉ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ± + ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΠΎ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Ρ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ²ΡΠ΅Π΄Π½Π΅Π²Π½ΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠΈ.ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ:β’Β Β Β Β Β Β Β Β Β Β Β Β ΠΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΡ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ±Π° ΠΈ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠ° ΠΎΠ΄ΠΎΠ±ΡΠ΅Π½Π° Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ, ΡΠ΅ΡΡΠ°ΠΊΡΠ΅ΡΠ½ΡΠΌ ΠΊ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·, Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π²ΡΡΠΎΠΊΠΈΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΎΠ±ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ°, Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ Π±Π΅Π· ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ.β’Β Β Β Β Β Β Β Β Β Β Β Β ΠΡΠΎΡΠΈΠ»Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΡΡΠΎΠΉ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Π²ΠΊΠ»ΡΡΠ°Π΅Ρ Π²ΡΡΠΎΠΊΡΡ ΡΠ°ΡΡΠΎΡΡ ΠΎΠ±ΡΠΈΡ
ΠΈ ΡΡΠΆΠ΅Π»ΡΡ
Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ²Π»Π΅Π½ΠΈΠΉ, ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΌΠ½ΠΎΠ³ΠΈΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ Π½ΡΠΆΠ΄Π°ΡΡΡΡ Π² ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠΈ Π΄ΠΎΠ·Ρ ΠΈΠ»ΠΈ ΠΏΡΠ΅ΠΊΡΠ°ΡΠ΅Π½ΠΈΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ. ΠΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ ΠΌΠΎΠΆΠ΅Ρ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°ΡΡ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΠΎΠ΄Π½ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ Π·Π°ΡΠΈΡΠ°Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡ Π½Π΅ΠΎΠΏΡΠ°Π²Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π²ΡΠ΅Π΄Π°.β’Β Β Β Β Β Β Β Β Β Β Β Β Π ΡΡΠΎΠΉ ΡΡΠ°ΡΡΠ΅ ΠΌΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΠ»ΠΈ ΠΌΡΠ»ΡΡΠΈΠ΄ΠΈΡΡΠΈΠΏΠ»ΠΈΠ½Π°ΡΠ½ΡΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ ΠΏΠΎ ΠΊΠΎΠ½ΡΡΠ»ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈ Π»ΠΈΡ, ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΡΡΠΈΡ
ΡΡ
ΠΎΠ΄ Π·Π° Π½ΠΈΠΌΠΈ, ΠΏΠ΅ΡΠ΅Π΄ Π½Π°ΡΠ°Π»ΠΎΠΌ Π»Π΅ΡΠ΅Π½ΠΈΡ Π»Π΅Π½Π²Π°ΡΠΈΠ½ΠΈΠ±ΠΎΠΌ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠΎΠΌ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΠΎ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Ρ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ²ΡΠ΅Π΄Π½Π΅Π²Π½ΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠΈ.ΠΡΠ±Π»ΠΈΠΊΡΠ΅ΡΡΡ Π½Π° ΡΡΡΡΠΊΠΎΠΌ ΡΠ·ΡΠΊΠ΅ Ρ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ Π°Π²ΡΠΎΡΠΎΠ². ΠΡΠΈΠ³ΠΈΠ½Π°Π»: Grande E., Glen H., Aller J. et al. Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma. Expert Opinion on Drug Safety 2017. DOI: 10.1080/14740338.2017.1380624
p.Ala541Thr variant of MEN1 gene: A non deleterious polymorphism or a pathogenic mutation?
Context
Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited syndrome, related to mutations in the MEN1 gene. Controversial data suggest that the nonsynonymous p.Ala541Thr variant, usually considered as a non-pathogenic polymorphism, may be associated with an increased risk of MEN1-related lesions in carriers.
Objective
The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes.
Patients and methods
We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1β heterozygous knock-out mice, and compared with wild type (WT).
Results
The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein.
Conclusion
Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype
TNM Staging of Neoplasms of the Endocrine Pancreas: Results From a Large International Cohort Study
Background Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. Methods The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. Results Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. Conclusion Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practic
Prognostic value of the neutrophil/lymphocyte ratio in enteropancreatic neuroendocrine tumors
Accessible prognostic tools are needed to individualize treatment of neuroendocrine tumors (NETs). Data suggest neutrophil/lymphocyte ratios (NLRs) have prognostic value in some solid tumors, including NETs. In the randomized double-blind CLARINET study (NCT00353496; EudraCT 2005-004904-35), the somatostatin analog lanreotide autogel/depot increased progression-free survival (PFS) compared with placebo in patients with inoperable or metastatic intestinal and pancreatic NETs (grades 1β2, Ki-674; n=25)]. Furthermore, NLRs were not prognostic in Cox models, irrespective of subgroups used. The therapeutic effect of lanreotide autogel/ depot 120mg was independent of NLRs (P>0.1). These exploratory post-hoc analyses in patients with advanced intestinal and pancreatic NETs contrast with previous data suggesting NLR has prognostic potential in NETs. This may reflect the inclusion of patients with lower-grade tumors or use of higher NLR cutoff values in the current analysis
Gastric Juvenile Polyposis with High-Grade Dysplasia in Pachydermoperiostosis
Pachydermoperiostosis (PDP) is the primary form of hypertrophic osteoarthropathy. It is a very rare disease consisting of pachydermia, digital clubbing and radiologic periostosis. Various digestive symptoms in PDP are seen in 11β49% of patients and juvenile polyps may be found at gastric endoscopy. We report here the history of a patient with PDP who was referred for assessment of severe anemia. Endoscopy of the upper digestive tract showed multiple polyps of the stomach with two huge lesions exhibiting foci of high-grade dysplasia. This observation suggests that PDP can be considered as a precancerous condition of the stomach and systematic screening using endoscopy should be considered in these patients
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