Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer

2020 ◽  
Vol 38 (34) ◽  
pp. 4010-4018 ◽  
Author(s):  
Renaud Garrel ◽  
Gilles Poissonnet ◽  
Antoine Moyà Plana ◽  
Nicolas Fakhry ◽  
Gilles Dolivet ◽  
...  
Keyword(s):  
Sentinel Node ◽  
Hospital Stay ◽  
Standard Of Care ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Node Dissection ◽  
Neck Node ◽  
Neck Lymph Node ◽  
Median Hospital Stay ◽  
Oral And Oropharyngeal Cancer

PURPOSE Sentinel node (SN) biopsy is accurate in operable oral and oropharyngeal cT1-T2N0 cancer (OC), but, to our knowledge, the oncologic equivalence of SN biopsy and neck lymph node dissection (ND; standard treatment) has never been evaluated. METHODS In this phase III multicenter trial, 307 patients with OC were randomly assigned to (1) the ND arm or (2) the SN arm (experimental arm: biopsy alone if negative, or followed by ND if positive, during primary tumor surgery). The primary outcome was neck node recurrence-free survival (RFS) at 2 years. Secondary outcomes were 5-year neck node RFS, 2- and 5-year disease-specific survival (DSS), and overall survival (OS). Other outcomes were hospital stay length, neck and shoulder morbidity, and number of physiotherapy prescriptions during the 2 years after surgery. RESULTS Data on 279 patients (139 ND and 140 SN) could be analyzed. Neck node RFS was 89.6% (95% CI, 0.83% to 0.94%) at 2 years in the ND arm and 90.7% (95% CI, 0.84% to 0.95%) in the SN arm, confirming the equivalence with P < .01. The 5-year RFS and the 2- and 5-year DSS and OS were not significantly different between arms. The median hospital stay length was 8 days in the ND arm and 7 days in the SN arm ( P < .01). The functional outcomes were significantly worse in the ND arm until 6 months after surgery. CONCLUSION This study demonstrated the oncologic equivalence of the SN and ND approaches, with lower morbidity in the SN arm during the first 6 months after surgery, thus establishing SN as the standard of care in OC.

Reduction in Initial Length of Stay with Rivaroxaban Single-Drug Regimen versus LMWH-VKA Standard of Care: Findings from the EINSTEIN Trial Program

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3419-3419 ◽  
Author(s):  
Bonno van Bellen ◽  
Martin Prins ◽  
Luke Bamber ◽  
Maria Wang ◽  
Anthonie WA Lensing
Keyword(s):  
Hospital Stay ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Phase Iii ◽  
Treatment Burden ◽  
Median Length ◽  
Open Label ◽  
Parenteral Treatment ◽  
Single Drug ◽  
Long Term Treatment

Abstract Abstract 3419 Background The current standard of care for the treatment of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) is parenteral low molecular weight heparin (LMWH) or fondaparinux, overlapping with and followed by a vitamin K antagonist (VKA). According to guidelines, parenteral treatment should be discontinued only when patients have reached a stable level of anticoagulation with a VKA; defined as 2 consecutive measurements of international normalized ratio (INR) >2.0 at least 24 hours apart. Compared with the previous standard of care, continuous infusion of unfractionated heparin, LMWH has made outpatient treatment feasible and lowered the treatment burden for patients, while reducing healthcare system costs. However, based on local practice or initial severity of disease many patients, especially those with PE, are still hospitalized, with discharge delayed until parenteral treatment can be discontinued. Rivaroxaban is an oral anticoagulant that produces stable levels of anticoagulation without the need for dose adjustments or routine coagulation monitoring for acute or long-term treatment. With its oral mode of administration and without the need for parenteral bridging therapy, rivaroxaban has the potential to allow discharge based on a patient's clinical condition without the additional requirement of achieving adequate oral anticoagulation levels, thereby further reducing healthcare costs and increasing convenience for patients. Aims We investigated the potential of rivaroxaban to reduce the length of initial hospitalization and the proportion of patients hospitalized, using data from the EINSTEIN DVT and EINSTEIN PE studies. Methods The EINSTEIN DVT and EINSTEIN PE studies were large, open-label, randomized, non-inferiority phase III trials comparing oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with dose-adjusted subcutaneous enoxaparin (1.0 mg/kg twice daily) overlapping with, and followed by, warfarin or acenocoumarol (INR 2.0–3.0). There were no instructions in the protocols of the studies with regard to hospital admission and/or discharge, which were left to the judgment of the attending physician. Length of hospital stay was evaluated from investigator records of dates of admission and discharge. All analyses were carried out in the intention-to-treat population using the van Elteren test, a stratified non-parametric test of significance, stratified by intended treatment duration. Analyses were exploratory with no adjustments for multiplicity. Results In the EINSTEIN DVT trial, 1781 of 3449 (52%) patients were hospitalized for the qualifying event, with similar proportions in each treatment arm (Table). However, the median length of hospital stay was significantly shorter in the rivaroxaban arm compared with the enoxaparin/VKA arm (5.0 vs 8.0 days; p<0.0001). In the EINSTEIN PE trial, 4328 of 4832 (90%) patients were hospitalized, with similar proportions in each treatment arm. Again, the median length of hospital stay was significantly shorter in patients receiving rivaroxaban than in patients receiving enoxaparin/VKA (6.0 vs 7.0 days; p<0.0001). Conclusion These results indicate that a single-drug anticoagulation regimen using rivaroxaban significantly reduces the length of hospital stay for patients admitted for DVT and/or PE, relative to standard of care. This has the potential to reduce the treatment burden for patients and healthcare systems. Disclosures: van Bellen: Bayer Brazil: Membership on an entity's Board of Directors or advisory committees. Prins:Bayer Healthcare: Consultancy, Honoraria. Bamber:Bayer Healthcare: Employment. Wang:Bayer Healthcare: Employment. Lensing:Bayer Healthcare: Employment.

scholarly journals CLRM-07. INCREASING EFFICIENCY IN EARLY PHASE MULTICENTER IMAGING BIOMARKER TRIALS: EMERGING STRATEGIES FROM THE GABLE (GLIOBLASTOMA ACCELERATED BIOMARKER LEARNING ENVIRONMENT) TRIAL

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv2-iv2
Author(s):  
Daniel Barboriak ◽  
Jon Steingrimsson ◽  
Constantine Gatsonis ◽  
David Schiff ◽  
Lawrence Kleinberg
Keyword(s):  
Learning Environment ◽  
Planning Process ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Evaluation Strategy ◽  
Multicenter Trials

Abstract Validated biomarkers that more accurately predict prognosis and/or measure disease burden in patients with high-grade gliomas would help triage which treatment strategies are most promising for evaluation in Phase III multicenter trials. Multicenter trials to evaluate imaging biomarkers in this group face particular challenges; these trials have historically been slow to accrue and have not recently succeeded in validating new imaging biomarkers useful in treatment development. Due to variability in image acquisition protocols, scanner hardware, image analysis, and interpretive schemes, promising results obtained in single centers are poor predictors of success in the multicenter setting. Multicenter preliminary data to support further evaluation of imaging biomarkers is rarely available. The need for more efficient trial designs that bring multicenter data earlier into the process of biomarker development has become increasingly clear. In this presentation, the planning process within ECOG-ACRIN’s Brain Tumor Working Group for a platform multicenter trial called GABLE (Glioblastoma Accelerated Biomarker Learning Environment trial) designed to evaluate biomarkers for distinguishing pseudoprogression from true progression in patients with newly diagnosed GBM is described. In our planning process, it was determined that efficiencies can be gained from evaluating multiple biomarker types in parallel rather than serially; in the context of the proposed trial, not only conventional imaging biomarkers but plasma biomarkers and radiomic biomarkers can be evaluated simultaneously. Patient tolerance limits the feasibility of evaluating multiple non-standard-of-care imaging biomarkers in parallel. For this group of biomarkers, a “fast-switching” serial evaluation strategy using multiple interim analyses was developed to triage out biomarkers unlikely to succeed in identifying patient groups with clinically significant differences in median survival. For biomarker triage, an endpoint of event-free survival (events of either death or NANO progression) was proposed. Simulations were used to evaluate alpha and beta error using this evaluation strategy.

Results of interim analysis of the multicenter randomized phase III SENORITA trial of laparoscopic sentinel node oriented, stomach-preserving surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4028-4028 ◽  
Author(s):  
Keun Won Ryu ◽  
Young Woo Kim ◽  
Jae Seok Min ◽  
Hong Man Yoon ◽  
Ji Yeong An ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Early Gastric Cancer ◽  
Sentinel Node ◽  
Lymph Node Dissection ◽  
Interim Analysis ◽  
Phase Iii ◽  
Complication Rates ◽  
Node Dissection

4028 Background: The benefits and hazards of laparoscopic sentinel node oriented stomach-preserving surgery, compared to those of laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of laparoscopic sentinel node oriented stomach-preserving surgery in EGC. Methods: Other than those with absolute indication for endoscopic resection, eligible patients had EGC confined to the mucosa and submucosa, with diameter ≤ 3cm, regardless of histology on preoperative evaluation. Patients were randomized for laparoscopic standard gastrectomy or laparoscopic stomach-preserving surgery. Patients were stratified based on depth (mucosa vs. submucosa) and size (≤ 2cm vs. 2 < ≤ 3cm) of the EGC and by participating institution. The primary endpoint was 3-year disease-free survival (3yDFS). The expected 3yDFS was 97% and non-inferior margin was 5%. 580 patients and 24 events were needed to show non-inferiority with 80% power. One interim analysis was planned after 12 events (50%) occurred. Using the O’Brien-Fleming error spending function, the two-sided nominal significance level for the interim analysis would be 0.0054. Results: From March 2013 to May 2016 462 patients were randomized; analysis was performed in 421 after a dropout of 41 patients. Laparoscopic stomach-preserving surgery was possible in 75.6% by study protocol. Interim analysis was conducted based on 12 events (median follow-up: 15.89 months). The 3yDFS in the laparoscopic standard gastrectomy arm was 96%; the 3yDFS in the laparoscopic stomach-preserving surgery arm was 93%, (99.46% CI: -3.18%, 9.18%). The postoperative complication rates were 15.0% and 12.9%, respectively (p = 0.542). Conclusions: In this interim analysis, laparoscopic sentinel node oriented stomach-preserving surgery did not show non-inferiority for 3yDFS. The follow-up time was not mature enough to evaluate non-inferiority. Further follow-up will elucidate the role of laparoscopic sentinel node oriented stomach-preserving surgery. Clinical trial information: NCT01804998.

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