scholarly journals How Safe Is Arteriovenous Malformation Surgery? A Prospective, Observational Study of Surgery As First-Line Treatment for Brain Arteriovenous Malformations

Neurosurgery ◽  
2010 ◽  
Vol 66 (3) ◽  
pp. 498-505 ◽  
Author(s):  
Andrew S. Davidson ◽  
Michael K. Morgan
Keyword(s):  
Arteriovenous Malformations ◽  
Prospective Observational Study ◽  
First Line ◽  
Surgical Risk ◽  
Brain Arteriovenous Malformations ◽  
High Surgical Risk ◽  
Martin Grade ◽  
Eloquent Cortex ◽  
Grade 3 ◽  
First Line Treatment

Abstract OBJECTIVES Existing studies reporting the risk of surgery for brain arteriovenous malformations (AVMs) are often biased by the exclusion of patients not offered surgery. In this study, we examine the risk of surgery, including cases excluded from surgery because of the high surgical risk. METHODS Data were collected on 640 consecutively enrolled AVMs in a database that included all patients not considered for surgery. RESULTS Patients with Spetzler-Martin grade 1 to 2 AVMs (n = 296) were treated with a surgical risk of 0.7% (95% confidence interval [CI], 0%-3%); patients with Spetzler-Martin grade 3 to 4 AVMs in noneloquent cortex (n = 65) were treated with a surgical risk of 17% (95% CI, 10%-28%). Patients with Spetzler-Martin grade 3 to 5 AVMs in eloquent cortex (n = 168) were treated with a surgical risk of 21% (95% CI, 15%-28%). However, because 14% of patients in this series with similar AVMs were refused surgery because of perceived surgical risk, these results are not generalizable to the population of patients with similar AVMs. CONCLUSION The results of this series suggest that it is reasonable to offer surgery as a preferred treatment option for Spetzler-Martin grade 1 to 2 AVMs. This study also reinforces the predictive value of the Spetzler-Martin grading system, with some caveats.

Surgery for Unruptured Spetzler-Martin Grade 3 Brain Arteriovenous Malformations

Neurosurgery ◽  
2015 ◽  
Vol 77 (3) ◽  
pp. 362-370 ◽  
Author(s):  
Michael Kerin Morgan ◽  
Nazih Assaad ◽  
Miikka Korja
Keyword(s):  
Neurological Deficit ◽  
Arteriovenous Malformations ◽  
Late Recurrence ◽  
Adverse Outcomes ◽  
Brain Arteriovenous Malformations ◽  
Complete Obliteration ◽  
Martin Grade ◽  
Grade 3 ◽  
Permanent Neurological Deficit

Abstract BACKGROUND: There is uncertainty regarding the management of unruptured Spetzler-Martin grade 3 brain arteriovenous malformations (SMG3 ubAVM). OBJECTIVE: To analyze our series of patients treated by surgery. METHODS: A single-surgeon database of consecutively enrolled bAVMs (between 1989 and 2014) was analyzed. Adverse outcomes due to surgery were assigned within the first 6 weeks following surgery and outcome was prospectively recorded and assigned at the last follow-up visit by using modified Rankin Scale (mRS) score. RESULTS: Of the 137 reviewed patients, 112 (82%) were treated by surgery, 15 (11%) were treated elsewhere or by radiosurgery, and 10 (7%) were recommended for conservative management. Surgery for SMG3 ubAVM was associated with adverse outcomes with a new permanent neurological deficit of mRS >1 in 23 of 112 (21%) patients. Permanent neurological deficit leading to a mRS >2 from surgery was 3.6% (95% confidence interval, 1.1%-9.1%). Late recurrence of a bAVM occurred in 3 of 103 (2.9%) patients who had complete obliteration of bAVM confirmed immediately after surgery and who were subsequently later followed with radiological studies during the mean follow-up period of 3.0 years (range, 6 days to 18.8 years). CONCLUSION: When discussing surgical options for SMG3 ubAVM, a thorough understanding of the significance and incidence of adverse events and outcomes is required to fully inform patients. For our series, the additional subclassification of SMG ubAVM (based on variables contributing to the SMG or age) would not have been of use.

A Global Vascular Guidelines–Based Bypass-Preferred Population and Their Surgical Risk Among CLTI Patients Treated With Endovascular Therapy in a Real-World Practice

2020 ◽  
Vol 27 (4) ◽  
pp. 608-613
Author(s):  
Shin Okamoto ◽  
Osamu Iida ◽  
Mitsuyoshi Takahara ◽  
Yosuke Hata ◽  
Mitsutoshi Asai ◽  
...  
Keyword(s):  
Decision Tree ◽  
Endovascular Therapy ◽  
Mortality Risk ◽  
Bypass Surgery ◽  
Recursive Partitioning ◽  
First Line ◽  
Surgical Risk ◽  
High Surgical Risk ◽  
Infection Stage ◽  
First Line Treatment

Purpose: To determine in a chronic limb-threatening ischemia (CLTI) population who underwent endovascular therapy (EVT) how many patients would have been categorized as preferred for bypass surgery according to the Global Vascular Guidelines (GVG) and ascertain their surgical risk. Materials and Methods: The current study analyzed 1043 CLTI patients who presented WIfI (wound, ischemia, and foot infection) stage ≥2 and underwent EVT between April 2010 and December 2017. Of these, 176 were excluded for lack of angiographic or other data, leaving 867 CLTI patients (mean age 74±10 years; 523 men) for stratification according to the GVG into bypass-preferred, indeterminate, or EVT-preferred groups. The GVG recommend bypass as the first-line treatment when the wound is severe (WIfI stage ≥3) and lesions are complex (GLASS stage III). Surgical risk was estimated using the modified PREVENT III risk score. To further stratify the bypass-preferred population according to mortality risk, a survival decision tree was constructed using recursive partitioning. Results: The bypass-preferred group accounted for 55% [95% confidence interval (CI) 51% to 58%] of the overall population. The decision tree analysis extracted a low-mortality risk subgroup with a survival rate of 99% (95% CI 98% to 100%) at 1 month and 80% (95% CI 73% to 87%) at 2 years. According to the PREVENT III score, 34% (95% CI 27% to 42%) of the low mortality risk subgroup were classified as high surgical risk. Conclusion: A high proportion of patients undergoing EVT were considered bypass preferred based on the GVG, and the survival of these patients was not significantly different whether they were high or low surgical risk.

Multimodality Management of Spetzler-Martin Grade 3 Brain Arteriovenous Malformations with Subgroup Analysis

2017 ◽  
Vol 102 ◽  
pp. 263-274 ◽  
Author(s):  
Isaac Josh Abecassis ◽  
John D. Nerva ◽  
Abdullah Feroze ◽  
Jason Barber ◽  
Basavaraj V. Ghodke ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Arteriovenous Malformations ◽  
Brain Arteriovenous Malformations ◽  
Martin Grade ◽  
Grade 3

scholarly journals Current surgical results with low-grade brain arteriovenous malformations

2015 ◽  
Vol 122 (4) ◽  
pp. 912-920 ◽  
Author(s):  
Matthew B. Potts ◽  
Darryl Lau ◽  
Adib A. Abla ◽  
Helen Kim ◽  
William L. Young ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Functional Outcomes ◽  
Arteriovenous Malformations ◽  
Preoperative Embolization ◽  
Low Grade ◽  
Cure Rate ◽  
Brain Arteriovenous Malformations ◽  
First Line Therapy ◽  
Delayed Hemorrhage ◽  
Martin Grade

OBJECT Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs—the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process. METHODS A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period. RESULTS Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0–1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs). CONCLUSIONS Surgery should be regarded as the “gold standard” therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

scholarly journals Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer

2019 ◽  
Vol 3 (12) ◽  
pp. 2295-2304 ◽  
Author(s):  
Lia Head ◽  
Katja Kiseljak-Vassiliades ◽  
Toshimasa J Clark ◽  
Hilary Somerset ◽  
Jonathan King ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Standard Of Care ◽  
Response Evaluation ◽  
Adrenocortical Cancer ◽  
First Line ◽  
Current Standard ◽  
Dismal Prognosis ◽  
Grade 3 ◽  
Combined Immunotherapy ◽  
First Line Treatment

Abstract Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.

The transvenous retrograde pressure cooker technique for the curative embolization of high-grade brain arteriovenous malformations

2020 ◽  
pp. neurintsurg-2020-016566
Author(s):  
Masaomi Koyanagi ◽  
Pascal John Mosimann ◽  
Hannes Nordmeyer ◽  
Markus Heddier ◽  
Juergen Krause ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
High Grade ◽  
Transvenous Embolization ◽  
Cure Rate ◽  
Brain Arteriovenous Malformations ◽  
Long Term Follow Up ◽  
Occlusion Rate ◽  
Grade 3

BackgroundTransvenous embolization of brain arteriovenous malformations (AVMs) can be curative. We aimed to evaluate the cure rate and safety of the transvenous retrograde pressure cooker technique (RPCT) using coils and n-butyl-2-cyanoacrylate as a venous plug.MethodsAll AVM patients treated via transvenous embolization between December 2004 and February 2017 in a single center were extracted from our database. Inclusion criteria were: inability to achieve transarterial cure alone; AVM < 3 cm; and single main draining vein. Outcome measures were immediate and 90 days' angiographic AVM occlusion rate, and morbidity and mortality at 30 days and 12 months, according to the modified Rankin Scale (mRS) score.ResultsFifty-one patients (20 women; median age 47 years) were included. A majority (71%) were high grade (3 to 5 in the Spetzler–Martin classification). AVMs were deeply seated in 30 (59%) and cortical in 21 patients (41%). Thirty-three patients were previously embolized transarterially (65%). All patients but one were cured within a single session with the RPCT (96%). Cure was confirmed on follow-up digital subtraction angiography at 3 months in 82% of patients. Three patients experienced intracranial hemorrhage (6%), one requiring surgical evacuation. There were no deaths. One treatment-related major permanent deficit was observed (2.0%). Mean mRS before treatment, at 30 days, and 12 months after RPCT was 1.5, 1.5, and 1.3, respectively.ConclusionsThe retrograde pressure cooker technique can be curative in carefully selected high-grade AVMs. Long-term follow-up and prospective studies are needed to confirm our results.

Bendamustine In Combination With Rituximab As First-Line Treatment For Indolent Non-Hodgkin Lymphoma: Retrospective Analysis Of An Spanish Registry

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5094-5094 ◽  
Author(s):  
Silvia Solorzano ◽  
Carmen Martinez-Chamorro ◽  
Carlos Panizo ◽  
Cristina Quero ◽  
Guillermo Deben ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Bone Marrow Involvement ◽  
Common Adverse Event ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Compassionate Use ◽  
First Line ◽  
Bulky Disease ◽  
Grade 3 ◽  
First Line Treatment

Abstract Introduction Indolent lymphomas represent 40% of all subtypes of non-Hodking's lymphoma, of which follicular lymphoma (FL) is the most frequent. Bendamustine is a dual alkylating agent with demonstrated high efficacy and low toxicity profile in reported clinical trials. We present the preliminary results from the experience of Spanish compassionate use registry of this agent as first-line treatment for indolent lymphoma. Methods Retrospective multicenter analysis of patients with indolent non-Hodgkin lymphomas (iNHL) treated as frontline with Bendamustine plus Rituximab (BR) in compassionate use. Clinical efficacy was evaluated according to Cheson criteria (2007) and toxicity according to CTCAE v3.0 scale. This study has been approved by local ethical committees. Results Patients’ characteristics: There are 96 patients registered (9 centers), with the following diagnoses: FL: 62 (64.5%), marginal zone 24 (25%), Waldenström macroglobulinemia 7 (7.3%) and mantle NHL 3 (3.1%). The main clinical features of the series are: 45% males, median age 64 years (range 36-84), 87.1% ECOG≤ 1, 63% Ann Arbor stage IV, 50.5% high risk FLIPI and 43.7% CIRS ≥ 4. Extranodal involvement was present in 79.1% of the patients, bone marrow  involvement in 52% and 11 patients (11.9%) had bulky disease. Treatment consisted in 6 cycles of BR (B-90 mg/m2 D1-2, R-375mg/m2 D1) in 95% patients. Median number of cycles administrated was 6 (range 1-8). G-CSF support was administered in 16.1% of cycles. Response and Safety: Overall response rate was 95%, with 65.5 % CR, 13.1% uCR and 16.4% PR in the 61 evaluable patients. Progression was documented in 4.9% of patients. Three exitus ocurred due to aspergillosis, progression and other not related with LNH. Median follow-up period was 14 months (3-47). In general, treatment was well tolerated; over 461 cycles registered, the most common adverse event was hematological toxicity with grade 3-4 neutropenia in 10.4%, grade 3-4 leucocitopenia in 6.9% and grade 3-4 anemia in 1.9% of the cycles. Other toxicities included all grades infections in 3.2% of patients, gastrointestinal in 3.4%, asthenia in 3.2%, chills in 1.1%, and mucositis 0.4%. Only 9 hospitalizations due to febrile neutropenia were reported. Conclusion Bendamustine plus rituximab was an effective and well tolerated regimen for newly diagnosed patients with indolent NHL. Disclosures: No relevant conflicts of interest to declare.

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