Encephaloduroarteriosynangiosis Averts Stroke in Atherosclerotic Patients With Border-Zone Infarct: Post Hoc Analysis From a Performance Criterion Phase II Trial

Neurosurgery ◽  
2021 ◽  
Vol 89 (Supplement_2) ◽  
pp. S111-S111
Author(s):  
Miguel D Quintero-Consuegra ◽  
Juan F Toscano ◽  
Robin Babadjouni ◽  
Peyton Nisson ◽  
Mohammad N Kayyali ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Criterion ◽  
Border Zone ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
A Performance

Overall survival after 177Lu-PSMA-617 molecular radiotherapy in patients with metastatic castrate-resistant prostate cancer: Post-hoc analysis of a prospective phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5549-5549 ◽  
Author(s):  
Jeremie Calais ◽  
Jeannine Gartmann ◽  
Wesley R Armstrong ◽  
Pan Thin ◽  
Kathleen Nguyen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Post Hoc Analysis ◽  
Molecular Radiotherapy ◽  
Prospective Phase ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Post Hoc

5549 Background: This was an open-label randomized prospective bi-centric single-arm phase II clinical trial of 177Lu-PSMA-617 molecular radiotherapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) conducted at University of California Los Angeles (USA) and Excel Diagnostics & Nuclear Oncology Center (Houston, TX, USA) (NCT03042312). The study was investigator-initiated under an investigational new drug approval protocol (IND#133661) with authorization of charging for investigational drug (cost-recovery, Title 21 CFR 312.8). We report here the post-hoc analysis of overall survival (OS) in a single-study site cohort (UCLA). Methods: Patients with progressive mCRPC (biochemical, radiographic, or clinical) after ≥1 novel androgen axis drug (NAAD), either chemotherapy (CTX) naïve or post-CTX, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA-target expression by PET were eligible. Patients received up to 4 cycles of 177Lu-PSMA-617 every 8±1 weeks and were randomized into 2 treatment activities groups (6.0 or 7.4 GBq). Efficacy was defined as serum PSA decline of ≥50% from baseline and served as primary endpoint (hypothesis: ≥40% of responders after 2 cycles). Results: 43 patients were randomized to the 6.0 GBq (n= 14) and 7.4 GBq (n=29) treatment arms. 11/43 (26%) were CTX naïve while 10/43 (23%), 12/43 (28%), 5/43 (12%) and 5/43 (12%) had received 1, 2, 3 or 4 CTX regimens. Median baseline PSA was 29.2 ng/ml (mean 228.8, range 0.5-2082.6). 21/43 (49%) completed 4 cycles of 177Lu-PSMA-617 whereas 4/43 (9%), 13/43 (30%) and 5/43 (12%) underwent 1, 2 and 3 cycles. PSA decline of ≥50% was observed in 11/43 of patients (26%) after 2 cycles and in 16/43 (37%) at any time (best PSA response). 9/43 (21%) had a PSA decline of ≥90% and 23/43 (53%) had any PSA decline (>0%). After a median follow-up of 19.5 months the median OS was 14.8, 15.7 and 13.5 months in the whole cohort, the 6.0 GBq and 7.4 GBq treatment arms, respectively (p=0.68). Patients showing a PSA decline of ≥50% after 2 cycles and at any time had a longer OS: median 20.1 months vs. 13.6 (p=0.091) and 20.1 vs. 11.6 (p=0.002), respectively. Conclusions: In this post-hoc analysis of a single-site cohort of 43 patients included in a prospective phase II trial the median OS after 177Lu-PSMA-617 molecular radiotherapy in patients with progressive mCRPC was 14.8 months. There was no difference of efficacy between the 6.0 GBq and 7.4 GBq treatment arms. Clinical trial information: NCT03042312 .

scholarly journals 32.3 A POST-HOC ANALYSIS EXPLORING PARTICIPANT-LEVEL TRAJECTORIES OF COGNITIVE PERFORMANCE AMONG PATIENTS WITH SCHIZOPHRENIA IN A MULTI-NATIONAL PHASE II TRIAL

2019 ◽  
Vol 45 (Supplement_2) ◽  
pp. S142-S142
Author(s):  
Kiri Granger ◽  
Jack Cotter ◽  
Elizabeth Baker ◽  
Jenny Barnett ◽  
Michael Sand
Keyword(s):  
Cognitive Performance ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Interfractional Geometric Variations and Dosimetric Benefits of Stereotactic MRI Guided Online Adaptive Radiotherapy (SMART) of Prostate Bed after Radical Prostatectomy: Post-Hoc Analysis of a Phase II Trial

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2802
Author(s):  
Minsong Cao ◽  
Yu Gao ◽  
Stephanie M. Yoon ◽  
Yingli Yang ◽  
Ke Sheng ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Maximum Dose ◽  
Adaptive Radiotherapy ◽  
Prostate Bed ◽  
Similar Coefficient ◽  
Mri Guided ◽  
Post Hoc ◽  
Shape Changes

Purpose: To evaluate geometric variations of patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and the dosimetric benefits of stereotactic MRI guided adaptive radiotherapy (SMART) to compensate for these variations. Materials/Methods: The CTV and OAR were contoured on 55 MRI setup scans of 11 patients treated with an MR-LINAC and enrolled in a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum preparation protocols and received five fractions of 6−6.8 Gy to the prostate bed. Interfractional changes in volume were calculated and shape deformation was quantified by the Dice similar coefficient (DSC). Changes in CTV-V95%, bladder and rectum maximum dose, V32.5Gy and V27.5Gy were predicted by recalculating the initial plan on daily MRI. SMART was retrospectively simulated if the predicted dose exceeded pre-set criteria. Results: The CTV volume and shape remained stable with a median volumetric change of 3.0% (IQR −3.0% to 11.5%) and DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median −24.5%, IQR −34.6% to 14.5%) and rectum (median 5.4%, IQR − 9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.73, respectively). The median CTV-V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, SMART would have been deemed beneficial for 78.2% of the 55 fractions based on target undercoverage (16.4%), exceeding OAR constraints (50.9%), or both (10.9%). Simulated SMART improved the dosimetry and met dosimetric criteria in all fractions. Moderate correlations were observed between the CTV-V95% and target DSC (R2 = 0.73) and bladder mean dose versus volumetric changes (R2 = 0.61). Conclusions: Interfractional dosimetric variations resulting from anatomic deformation are commonly encountered with post-prostatectomy RT and can be mitigated with SMART.

scholarly journals ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi16-vi17
Author(s):  
Roberta Rudà ◽  
Alessia Pellerino ◽  
Andrea Pace ◽  
Carmine Maria Carapella ◽  
Cristina Dealis ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Response Rate ◽  
Long Term Results ◽  
Molecular Subgroups ◽  
Who Grade ◽  
Post Hoc Analysis ◽  
Grade Ii ◽  
Post Hoc ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking. PATIENTS AND METHODS A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency >50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction >50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted. CONCLUSIONS The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.

Quality-adjusted time without symptoms or toxicity (Q-TWiST) of patients with metastatic colorectal cancer (mCRC) treated with fruquintinib in a phase II clinical trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 765-765
Author(s):  
Jin Li ◽  
Ruihua Xu ◽  
Yuxian Bai ◽  
Jianming Xu ◽  
Tianshu Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Bootstrap Method ◽  
Progression Free Survival ◽  
Health States ◽  
Treatment Benefits ◽  
Kaplan Meier ◽  
Utility Coefficient ◽  
Post Hoc

765 Background: In a randomized phase II trial of mCRC patients who have failed at least 2 lines of standard therapy, fruquintinib has demonstrated superior progression free survival (PFS) and overall survival (OS) benefits over placebo. We further assessed the between-treatment difference of quality of life (QoL) using a Q-TWiST analysis, to elucidate the trade-off between adverse events and treatment benefits. Methods: Mean PFS and OS were estimated using the Kaplan-Meier method. OS in Q-TWiST analysis was partitioned into 3 health states: TOX (time with toxicity before progression), TWiST (time without symptoms or toxicity) and REL (time from progression until death). The algorism of Q-TWiST is the sum of the mean durations for the 3 health states, with each state weighted by its respective utility coefficient. The 95% confidence intervals of mean are calculated with z method and the standard error is generated by bootstrap method. The relative Q-TWiST gains of > = 10% and > = 15% are considered as a clinically important and clearly clinically important, respectively (Revicki, 2006). Results: A total of 71 patients were included in this post-hoc analysis. The 47 patients of fruquintinib arm had significant longer PFS, compared with the 24 patients in the placebo arm (mean: 5.0 vs. 2.2 months, difference [95% CI]: 2.8 [1.4, 4.3]). The benefit of OS was numerically superior (mean: 8.6 vs. 6.9 months, difference [95% CI]: 1.7 [-0.5, 4.0]). Patients treated with fruquintinib showed numerically longer overall Q-TWiST (mean: 5.8 vs. 4.4 months, difference [95% CI]: 1.4 [-0.1, 2.9] than those received placebo with the relative gain of 20.3% over OS, assuming the utility during TOX/REL period is 0.5 and that during the TWiST is 1.0. Sensitivity analysis demonstrated that the Q-TWiST gain may range from -0.7% to 41.2% at various utility assignments. Conclusions: In this phase II trial, mCRC patients treated with fruquintinib had clearly clinically important QoL benefit. Further studies with larger sample size are needed to confirm this finding. Clinical trial information: NCT02196688.

scholarly journals Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial

2020 ◽  
Vol 79 (4) ◽  
pp. 525-528 ◽  
Author(s):  
Felix Eckstein ◽  
Jeffrey L Kraines ◽  
Aida Aydemir ◽  
Wolfgang Wirth ◽  
Susanne Maschek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Healthy Subjects ◽  
Cartilage Thickness ◽  
Cartilage Loss ◽  
Thickness Change ◽  
Post Hoc Analysis ◽  
Registration Number ◽  
Osteoarthritis Initiative ◽  
Post Hoc ◽  
Femorotibial Joint

ObjectivesIn the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.MethodsPatients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.ResultsThinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.ConclusionsSprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.Trial registration numberNCT01919164.

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