scholarly journals Direct versus indirect bypass procedure for the treatment of ischemic moyamoya disease: results of an individualized selection strategy

2020 ◽  
pp. 1-12
Author(s):  
Troels H. Nielsen ◽  
Kumar Abhinav ◽  
Eric S. Sussman ◽  
Summer S. Han ◽  
Yingjie Weng ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Study Endpoint ◽  
Selection Strategy ◽  
Primary Study ◽  
Stroke Rate ◽  
Cerebrovascular Reserve ◽  
Perioperative Stroke ◽  
Bypass Procedure ◽  
Bypass Group ◽  
Direct Bypass

OBJECTIVEThe only effective treatment for ischemic moyamoya disease (iMMD) is cerebral revascularization by an extracranial to intracranial bypass. The preferred revascularization method remains controversial: direct versus indirect bypass. The purpose of this study was to test the hypothesis that method choice should be personalized based on angiographic, hemodynamic, and clinical characteristics to balance the risk of perioperative major stroke against treatment efficacy.METHODSPatients with iMMD were identified retrospectively from a prospectively maintained database. Those with mild to moderate internal carotid artery or M1 segment stenosis, preserved cerebrovascular reserve, intraoperative M4 segment anterograde flow ≥ 8 ml/min, or the absence of frequent and severe transient ischemic attacks (TIAs) or stroke had been assigned to indirect bypass. The criteria for direct bypass were severe ICA or M1 segment stenosis or occlusion, impaired cerebrovascular reserve or steal phenomenon, intraoperative M4 segment retrograde flow or anterograde flow < 8 ml/min, and the presence of frequent and severe TIAs or clinical strokes. The primary study endpoint was MRI-confirmed symptomatic stroke ≤ 7 days postoperatively resulting in a decline in the modified Rankin Scale (mRS) score from preoperatively to 6 months postoperatively. As a secondary endpoint, the authors assessed 6-month postoperative DSA-demonstrated revascularization, which was classified as < 1/3, 1/3–2/3, or > 2/3 of the middle cerebral artery territory.RESULTSOne hundred thirty-eight patients with iMMD affecting 195 hemispheres revascularized in the period from March 2016 to June 2018 were included in this analysis. One hundred thirty-three hemispheres were revascularized with direct bypass and 62 with indirect bypass. The perioperative stroke rate was 4.7% and 6.8% in the direct and indirect groups, respectively (p = 0.36). Degree of revascularization was higher in the direct bypass group (p = 0.03). The proportion of patients improving to an mRS score 0–1 (from preoperatively to 6 months postoperatively) tended to be higher in the direct bypass group, although the difference between the two bypass groups was not statistically significant (p = 0.27).CONCLUSIONSThe selective use of an indirect bypass procedure for iMMD did not decrease the perioperative stroke rate. Direct bypass provided a significantly higher degree of revascularization. The authors conclude that direct bypass is the treatment of choice for iMMD.

Abstract 136: Prediction of Postoperative Hyperperfusion by Intraoperative Assessment of Indocyanine Green Videoangiography in Moyamoya Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Haruto Uchino ◽  
Masaki Ito ◽  
Ken Kazumata ◽  
Naoki Nakayama ◽  
Satoshi Kuroda ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Moyamoya Disease ◽  
Flow Index ◽  
Emission Computed Tomography ◽  
Semiquantitative Analysis ◽  
Bypass Procedure ◽  
Before And After ◽  
Direct Bypass ◽  
Cortical Perfusion

Background: Postoperative hyperperfusion is a potential complication of the direct bypass procedure for moyamoya disease (MMD). However, no reliable modality is available yet for the prediction of postoperative hyperperfusion during surgery for MMD. This study aimed to investigate whether semiquantitative analysis of indocyanine green (ICG) videoangiography could contribute to the prediction of postoperative hyperperfusion in MMD. Methods: This study included 12 hemispheres from 10 patients who underwent surgical revascularization for MMD. Intraoperative ICG videoangiography was performed before and after a direct bypass procedure. The ICG intensity-time curves were semiquantitatively analyzed to evaluate cortical perfusion by calculating the blood flow index (BFI). Using single-photon emission computed tomography (SPECT), postoperative cerebral blood flow measurements were performed thrice: immediately and 2 and 7 days after surgery. Results: BFI significantly increased from 21.3 ± 10.5 to 38.4 ± 20.0 after bypass procedures in all the hemispheres (p < 0.01). The ratio of BFI before and after the bypass procedure was 2.4 ± 2.0, ranging from 0.5 to 8.0. Postoperative hyperperfusion was observed in 9 of the 12 operated hemispheres within 7 days after surgery. Of these, 3 hemispheres developed hyperperfusion immediately after surgery. In the adult cases, the increase in the ratio of BFI after bypass was significantly greater in those who developed hyperperfusion immediately after surgery than in those who did not (6.5 ± 0.5 vs. 1.8 ± 2.1, p < 0.01). In contrast, no significant increase in BFI was observed in the pediatric MMD patients who experienced immediate hyperperfusion. No correlation between the changes in BFI and the occurrence of delayed hyperperfusion was observed. Conclusions: Our results suggest that semiquantitative analysis of BFI by intraoperative ICG videoangiography is useful in evaluating changes in cortical perfusion after bypass procedures for MMD and can predict the occurrence of early-onset hyperperfusion in MMD patients after direct bypass.

135 Direct and Combined Revascularization Versus Indirect Revascularization in the Treatment of Moyamoya Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
K S Lee ◽  
M Teo ◽  
J J Y Zhang Zhang ◽  
G K Steinberg
Keyword(s):  
Systematic Review ◽  
Moyamoya Disease ◽  
Perioperative Complications ◽  
Meta Analysis ◽  
Adult Patients ◽  
Stroke Rate ◽  
Perioperative Mortality ◽  
Perioperative Stroke ◽  
Paediatric Patients ◽  
Indirect Revascularization

Abstract Introduction The goal of surgical revascularization of moyamoya disease (MMD) is to augment cerebral blood flow and prevent intracranial haemorrhage. This study aimed to compare direct and combined versus indirect bypasses with regard to perioperative complications in paediatric and adult patients with MMD, using a systematic review and meta-analysis of published observational studies. Method Primary outcome measures analysed included perioperative (30 days) complications. Results 20 studies reporting 2982 patients were eventually included. Pooled mean age was 37.5 years (95%CI: 33.5–41.5) and 7.4 years (95%CI: 4.1–10.7) in adult and paediatric patients, respectively. For adult patients, perioperative stroke rate was comparable between direct/combined and indirect bypass (OR = 1.26 [95%CI: 0.81–1.96], p = 0.300 for indirect). For paediatric patients, perioperative stroke rate was comparable between direct/combined and indirect bypass (OR = 2.43 [95%CI:0.74–7.94], p = 0.143 for indirect). No difference found in perioperative mortality between direct/combined and indirect bypass for adult patients (OR = 1.16 [95%CI:0.07–19.00], p = 0.915 for indirect). There was no difference in perioperative mortality between direct/combined and indirect bypass (OR = 1.39 [95%CI:0–Inf], p = 1.00 for indirect) in paediatric patients. Conclusions Both direct and indirect bypasses can be equally effective in preventing stroke, with similar rates of perioperative complications in paediatric and adult MMD patients.

scholarly journals P44 Direct and Combined Revascularization Versus Indirect Revascularization in the Treatment of Moyamoya Disease: A Systematic Review and Meta-Analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Keng Siang Lee ◽  
John J Y Zhang ◽  
Mario Teo ◽  
Gary K Steinberg ◽  
Keng Siang Lee
Keyword(s):  
Moyamoya Disease ◽  
Pediatric Patients ◽  
Perioperative Complications ◽  
Meta Analysis ◽  
Adult Patients ◽  
Stroke Rate ◽  
Perioperative Mortality ◽  
Perioperative Stroke ◽  
Significant Difference ◽  
Indirect Revascularization

Abstract Introduction There is currently no definite consensus regarding the surgical treatment of moyamoya disease (MMD). This study aimed to compare direct and combined versus indirect bypasses with regard to perioperative complications in pediatric and adult patients with MMD. Methods Systematic searches of Medline, Embase and Cochrane Central were undertaken. Primary outcome measures analyzed included perioperative complications defined as any major adverse events within 30 days after bypass surgery. Results 2490 studies were identified. 20 reporting 2982 patients were eventually included in our meta-analysis. Pooled mean age was 37.5 years (95%CI:33.5–41.5) and 7.4 years (95%CI:4.1–10.7) in adult and pediatric patients respectively. For adult patients, perioperative stroke rate was comparable between direct/combined bypass and indirect bypass (OR = 1.26 [95%CI:0.81–1.96], p = 0.300 for indirect bypass). For pediatric patients, perioperative stroke rate was comparable between direct/combined bypass and indirect bypass (OR = 2.43[95%CI:0.74–7.94], p = 0.143 for indirect bypass). No difference was found in perioperative mortality between direct/combined bypass and indirect bypass for adult patients (OR = 1.16[95%CI:0.07–19.00], p = 0.915 for indirect bypass). There was no difference in perioperative mortality between direct/combined bypass and indirect bypass (OR = 1.39 [95%CI:0 –Inf], p = 1.00 for indirect bypass) in pediatric patients. There was no significant difference in perioperative neurological deficit rates between direct/combined bypass and indirect bypass (OR = 1.27[95%CI:0.68–2.39], p = 0.451 for indirect bypass). Discussions/Conclusions Our meta-analysis provides statistical evidence suggesting that both direct and indirect bypasses can be equally effective in preventing stroke, with similar rates of perioperative complications in pediatric and adult patients.

scholarly journals Mortality after cardiopulmonary resuscitation on a medical ICU

2021 ◽  
Author(s):  
Richard Rezar ◽  
Bernhard Wernly ◽  
Michael Haslinger ◽  
Clemens Seelmaier ◽  
Philipp Schwaiger ◽  
...  
Keyword(s):  
Cardiopulmonary Resuscitation ◽  
Neurological Outcome ◽  
Cox Regression ◽  
Cerebral Performance Category ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Study Endpoint ◽  
Primary Study ◽  
Postresuscitation Care ◽  
Significant Difference

Summary Background Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA). Methods A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U‑tests and χ2-tests, for survival analysis both univariate and multivariable Cox regression were fitted. Results A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6‑month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35–1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU. Conclusion In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

403 Early results from a phase 1 study to evaluate safety, pharmacokinetics, and efficacy of AMG 404, a programmed death-1 (PD-1) antibody, in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A428-A428
Author(s):  
Timothy Price ◽  
Sant Chawla ◽  
Gerald Falchook ◽  
Hans Prenen ◽  
Iwona Lugowska ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Clear Cell ◽  
Phase 1 ◽  
Cell Cancer ◽  
Objective Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Advanced Solid Tumors

BackgroundEnhancement of antitumor immunity through inhibition of the checkpoint PD-1 receptor has been effective in the treatment of many malignancies. AMG 404 is a monoclonal antibody (mAb) targeting PD-1. This phase 1, open-label, multicenter first-in-human study (NCT03853109) will evaluate the safety, tolerability, pharmacokinetics, and efficacy of AMG 404 monotherapy in adult patients with advanced solid tumors.MethodsThe primary study endpoint is dose-limiting toxicity (DLT) and safety; key secondary endpoints include pharmacokinetic parameters, objective response rate (assessed Q8W), duration of response, and progression-free survival. Key inclusion criteria include histologically or cytologically proven metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation for which standard therapies have been exhausted or not available. Prior anti-PD-(L)1 or other checkpoint inhibitors were not allowed. Five dose-finding cohorts, including 2 expansion cohorts, ranged from 3–20 patients each. AMG 404 was given until disease progression, intolerance, or consent withdrawal.ResultsAs of the data cutoff date of May 4, 2020, 62 patients received at least 1 dose of AMG 404 and were included in the safety and efficacy analysis sets. Fifty percent were men, 72% had ECOG 1 performance status, median age was 62 years (range: 28–83), and 42% had ≥3 lines of prior anticancer therapy. Median AMG 404 exposure was ~3 months (maximum: ~12 months). No DLTs were observed. Treatment-related adverse events (TRAEs) were reported for 29 patients (47%): those reported for ≥2 patients were fatigue (n=7); hypothyroidism (n=6); increased blood thyroid stimulating hormone and nausea (n=4 each); increased aspartate aminotransferase, decreased appetite, and pyrexia (n=3 each); and increased alanine aminotransferase, arthralgia, diarrhea, and increased weight (n=2 each). AEs leading to withdrawal of AMG 404 were reported for 3 patients (5%); all were serious and considered to be not related to AMG 404. Sixteen (26%) patients died on study; no deaths were considered related to AMG 404. Preliminary pharmacokinetic results were consistent with those of other therapeutic anti-PD-1 mAbs. Three patients had a confirmed partial response (pancreatic cancer, clear cell cancer, and pleomorphic sarcoma); an additional 4 patients had one scan with a partial response and are pending a confirmatory scan (clear cell renal carcinoma, undifferentiated nasopharyngeal carcinoma, sarcomatoid carcinoma of unknown primary, and colon cancer).ConclusionsAMG 404 is tolerable at the tested doses with no DLTs reported. All observed TRAEs are consistent with other anti-PD-1 therapies. Encouraging anti-tumor activity has been observed in heavily pretreated patients. The study is continuing enrollment into additional cohorts.Trial RegistrationNCT03853109Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.

Challenging direct bypass surgery for very young children with moyamoya disease: technical notes

2021 ◽  
Author(s):  
Yoshio Araki ◽  
Kenji Uda ◽  
Kinya Yokoyama ◽  
Fumiaki Kanamori ◽  
Michihiro Kurimoto ◽  
...  
Keyword(s):  
Young Children ◽  
Moyamoya Disease ◽  
Bypass Surgery ◽  
Very Young Children ◽  
Direct Bypass

A phase 3 study to evaluate the efficacy and safety of tafasitamab plus lenalidomide and rituximab versus placebo plus lenalidomide and rituximab in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7568-TPS7568
Author(s):  
Laurie Helen Sehn ◽  
Christian W Scholz ◽  
Stefano Luminari ◽  
Antonio Salar ◽  
Bjorn E. Wahlin ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Benefit ◽  
B Cell Lymphoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Cns Lymphoma ◽  
Phase 2 ◽  
Phase 3 ◽  
Potential Clinical Benefit ◽  
Anti Cd20

TPS7568 Background: Most patients with the indolent non-Hodgkin lymphoma (NHL) subtypes FL or MZL respond to first-line treatment but relapse is common, and there is no single standard treatment for patients with R/R FL or MZL. Tafasitamab is an Fc-engineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B-cell proliferation via B-cell receptor signaling. In preclinical studies, tafasitamab has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). Tafasitamab monotherapy has shown promising clinical activity in a phase 2a study in patients with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in patients with FL and 33% (n/N = 3/9) in patients with MZL. In an ongoing phase 2, single-arm study (L-MIND, NCT02399085), tafasitamab plus LEN followed by tafasitamab alone demonstrated an ORR of 57.5% (n/N = 46/80) in patients with R/R diffuse large B-cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of tafasitamab plus LEN and rituximab for patients with R/R FL or MZL. Methods: This phase 3 double-blind, placebo-controlled, randomized study is designed to investigate whether tafasitamab plus LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in patients with R/R FL or R/R MZL. Patients will be randomized 1:1 to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) plus LEN (20 mg PO QD, days 1–21/ cycle for 12 cycles) and rituximab (375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or placebo (0.9% saline solution IV) plus LEN and rituximab. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for patients with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET-CR rate (INV) at end of treatment (4–8 weeks after last treatment) and OS in patients with FL. Inclusion criteria include age ≥18 y, histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including anti-CD20 refractory disease), ECOG PS ≤2, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab plus LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF < 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling patients; planned enrollment is 528 patients with R/R FL and 60–90 patients with R/R MZL. Clinical trial information: NCT04680052.

Preliminary results of phase 2 trial of preoperative image guided intensity modulated proton radiation therapy (IMPT) with simultaneously integrated boost (SIB) to the high-risk margin for retroperitoneal sarcomas (RPS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11550-11550
Author(s):  
Thomas F. DeLaney ◽  
John Thomas Mullen ◽  
Yen-Lin Chen ◽  
Ivy Ann Petersen ◽  
Andrew Justin Bishop ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Femoral Nerve ◽  
Study Endpoint ◽  
Primary Study ◽  
Tumor Control ◽  
Preoperative Radiation ◽  
X Rays ◽  
Lower Extremity Weakness ◽  
Disease Free

11550 Background: RPS often have local recurrence (LR) after surgery. Preoperative radiation (RT) to 50.4 Gy can reduce LR risk but is not uniformly effective, especially after (+) margin resections. Therefore, we conducted a multi-institutional, prospective Phase II study to assess efficacy and tolerability of preop IMPT with selective dose escalation to 63 GyRBE to the posterior RPS margin (clinical target volume [CTV] 2) at high risk for (+) margins to further reduce the risk of LR. This dose was tolerable in a prior phase I study (DeLaney T et al, 2017, PMID:28740917). Methods: Primary RPS patients (pts) >18 years received preop IMPT, 50.4 GyRBE in 28 fractions (fx) of 1.8 GyRBE to CTV1 (tumor plus adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 GyRBE in 28 fx of 2.25 GyRBE. Pts with high-grade tumors could get chemotherapy(CTX) prior to IMPT. To avoid treatment delay, 11 fx of IMRT x-rays could be substituted for IMPT. Pts had restaging and surgery 4-8 weeks after IMPT. Primary study endpoint was local tumor control. Secondary endpoints included clinical and pathologic response, surgical margin status, and disease-free and overall survival. Results: We accrued 60 pts from January 2016 to February 2021. Histology: 35 liposarcoma(LPS) (19 dediff and 16 well diff), 22 leiomyosarcoma(LMS), and 3 undifferentiated pleomorphic sarcoma. IMPT was delivered per protocol in all pts. 51 pts have had surgery, 5 are awaiting surgery, and 4 had no surgery due to metastases(DM) on preop imaging. 22 pts had (+) margins. 2 pts had > 75% necrosis. With 23-month median (range 1-52 months) follow-up after start of RT, there were two LRs. A dediff LPS pt had a well diff LPS LR 26 months postop, resected, and is disease-free. A renal vein/IVC LMS pt treated with CTX and IMPT had LR and DM 4 months postop and died from disease. Surgical Clavien-Dindo morbidity scores: 0(21), 1(9), 2(8), 3a (4), 3b(4), 4a(2), 4(b)1, 5(2); the periop deaths were from sepsis(pneumonia) and duodenal ulcer. The grade 3-4 periop morbidity included abscess(3), treated by catheter(2) or operative(1) drainage, prolonged hospital stays (2 pts with IVC LMS), small bowel obstruction (1), and late sigmoid colon anastomotic failure (1). Readmissions for lymphopenia(1), pneumoperitoneum (1), and volume overload (1). One late neuropathy was seen in a Type II diabetic pt with transient postop weakness after femoral nerve dissection who later had significant lower extremity weakness 3.75 years postop. Study was amended to reduce IMPT dose in diabetic pts. Conclusions: Preoperative IMPT with selective dose escalation to 63 GyRBE to the high risk posterior RPS margin is feasible. Early local control results with this approach appear promising. Some peri-operative morbidity was noted but appears to be in the expected range for RPS resections. Clinical trial information: NCT01659203.

Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11518-11518
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Dedifferentiated Liposarcoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Primary Analysis ◽  
European Organization ◽  
Experimental Drugs

11518 Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.

Early versus Delayed Extracranial-Intracranial Bypass Surgery in Symptomatic Atherosclerotic Occlusion

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 656-663 ◽  
Author(s):  
Cory J Rice ◽  
Sung-Min Cho ◽  
Ather Taqui ◽  
Nina Z Moore ◽  
Alex M Witek ◽  
...  
Keyword(s):  
Bypass Surgery ◽  
Hemorrhagic Stroke ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Inclusion Criteria ◽  
Short Term ◽  
Ischemic Event ◽  
Perioperative Stroke ◽  
Tertiary Referral Center ◽  
Bypass Group

Abstract Background Clinical trials of extracranial-intracranial (EC-IC) bypass surgery studied patients in subacute and chronic stage after ischemic event. OBJECTIVE To investigate the short-term outcomes of EC-IC bypass in progressive acute ischemic stroke or recent transient ischemic attacks. Methods The study was a retrospective review at a single tertiary referral center from 2008 to 2015. Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle cerebral artery. Early bypass group who underwent surgery within 7 d of last ischemic symptoms were compared to late bypass group who underwent surgery >7 d from last ischemic symptom. The primary endpoint was perioperative ischemic or hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery. Results Of 126 patients who underwent EC-IC bypass during the period, 81 patients met inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29) perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late bypass (P = .04). Of patients with acute stroke within 7 d of surgery, 41% (7/17) had perioperative stroke within 7 d (P = .07). Six of nine patients (67%) with blood pressure dependent fluctuation of neurologic symptoms had perioperative stroke (P = .049). Conclusion EC-IC bypass in setting of acute symptomatic stroke within 1 wk may confer higher risk of perioperative stroke. Patients undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms might be at highest risk for perioperative stroke.

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