Adverse Events in Neurosurgery: The Novel Therapy-Disability-Neurology Grade

Neurosurgery ◽  
2021 ◽  
Author(s):  
Alexis Paul Romain Terrapon ◽  
Costanza Maria Zattra ◽  
Stefanos Voglis ◽  
Julia Velz ◽  
Flavio Vasella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
External Validation ◽  
Neurological Deficits ◽  
Patient Centered ◽  
Novel Therapy ◽  
Karnofsky Performance Status Scale ◽  
Medical Centers ◽  
Standardized Report

Abstract BACKGROUND The most widely used classifications of adverse events (AEs) in neurosurgery define their severity according to the therapy used to treat them. This concept has substantial shortcomings because it does not reflect the severity of AEs that are not treated, such as new neurological deficits. OBJECTIVE To present a novel multidimensional and patient-centered classification of the severity of AE in neurosurgery and evaluate its applicability. METHODS The Therapy-Disability-Neurology (TDN) grading system classifies AEs depending on the associated therapy, disability, and neurological deficits. We conducted a 2-center retrospective observational study on 6071 interventions covering the whole neurosurgical spectrum with data prospectively recorded between 2013 and 2019 at 2 institutions from 2 countries. RESULTS Using the first patient cohort (4680 interventions), a positive correlation was found between severity of AE and LOS as well as treatment cost. Each grade was associated with a greater deterioration of the Karnofsky Performance Status Scale (KPS) at discharge and at follow-up. When using the same methods on the external validation cohort (1391 interventions), correlations between the grades of AE, LOS, and KPS at discharge were even more pronounced. CONCLUSION Our results suggest that the TDN grade is consistent with clinical and economic repercussions of AE and thus reflects AE severity. It is easily interpreted and enables comparison between different medical centers. The standardized report of the severity of AE in the scientific literature could constitute an important step forward toward a more critical, patient-centered, and evidence-based decision-making in neurosurgery.

scholarly journals Adverse Events in Surgical Neurology: The Novel Therapy-Disability-Neurology (TDN) Grade

2020 ◽  
Author(s):  
Alexis Paul Romain Terrapon ◽  
Costanza Maria Zattra ◽  
Stefanos Voglis ◽  
Julia Velz ◽  
Flavio Vasella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
External Validation ◽  
Length Of Hospital Stay ◽  
University Hospital ◽  
Grading System ◽  
Novel Therapy ◽  
Karnofsky Performance Status Scale ◽  
Neurologic Deficits

ABSTRACTBackgroundThe most widely used classifications of adverse events (AE) in surgical neurology assign a grade to AE that depends on the therapy used to treat them or on new neurologic deficits. Both concepts have substantial shortcomings in grading AE severity. We present a novel multidimensional approach to this challenge and aim at validating the new grading system.MethodsThe new Therapy-Disability-Neurology (TDN) grading system classifies AE into five grades, depending on the associated therapy, disability, and neurologic deficits. We conducted a two-center study on 6071 interventions covering the whole neurosurgical spectrum with data prospectively recorded between January 2013 and September 2019 at the University Hospital Zurich (USZ) and at the Fondazione IRCCS Istituto Neurologico Carlo Besta (FINCB).FindingsUsing data from USZ, a positive correlation was found between the severity of AE and the length of hospital stay (LOS) as well as treatment cost. Each grade was associated with a greater deterioration of the Karnofsky Performance Status Scale (KPS) at discharge and at follow-up. Additionally, there was a correlation between the severity of AE and absolute KPS values. When using the same methods on an external validation cohort from FINCB, correlations between the grade of AE, LOS, and KPS at discharge were even more pronounced.InterpretationOur results suggest that the TDN grade is consistent with clinical and economic repercussions of AE and thus reflects AE severity. It is objective, practical, easily interpreted, and enables comparison between different medical centers. The TDN grade will constitute an important step forward towards a more precise and standardized documentation of AE and ultimately lead to a more critical and patient-centered appraisal of process and outcome measures in surgical neurology.FundingNone.

scholarly journals Functional Outcome Following Synthetic Vertebral Body Implantation in the Management of Spinal Disorders

2020 ◽  
Vol 8 (B) ◽  
pp. 76-80
Author(s):  
Moneer K. Faraj ◽  
Bassam Mahmood Flamerz  Arkawazi ◽  
Hazim Moojid Abbas ◽  
Zaid Al-Attar
Keyword(s):  
Functional Outcome ◽  
Vertebral Body ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Spinal Tuberculosis ◽  
Vertebral Body Replacement ◽  
Spinal Tumors ◽  
Karnofsky Performance Status Scale ◽  
Significant Change

OBJECTIVE: Synthetic vertebral body replacement has been widely used recently to treat different spinal conditions affecting the anterior column. They arrange from trauma, infections, and even tumor conditions. In this study, we assess the functional outcome of this modality in different spinal conditions. PATIENTS AND METHODS: Thirty-six cases operated from October 2010 to December 2017. Twelve patients had spinal type A3 fractures, 11 cases with spinal tuberculosis (TB), and 13 cases with spinal tumors. They were followed clinically for a mean period of 2.4 years. RESULTS: All the cases were approached anteriorly. Seven cases had a post-operative infection. No neurological worsening reported. We had dramatic neurological improvement in all spinal TB cases. Mortality recorded in only 4 cases with metastatic spinal tumor during the mean period of follow-up. Karnofsky performance status scale showed statistically significant change for spinal TB, and tumor cases during the follow-up period, but there was no significant change in cases of spinal type A3 fractures. CONCLUSION: The positive outcome of this surgery makes it recommended for properly selected patients, especially with spinal TB and tumors.

Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and low Karnofsky performance status: Results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 315-315
Author(s):  
Thomas E. Hutson ◽  
Bradley Curtis Carthon ◽  
Jeffrey Yorio ◽  
Sunil Babu ◽  
Heidi Ann McKean ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Grade 3

315 Background: Combination therapy with nivolumab + ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability for patients (pts) with previously untreated advanced renal cell carcinoma (aRCC). Most pivotal clinical trials in pts with aRCC have excluded pts with low Karnofsky performance status (KPS; < 70%). CheckMate 920 is a multi-arm, phase IIIb/IV, open-label clinical trial of NIVO+IPI treatment in pts enrolled in a community practice setting with aRCC and a high unmet medical need. We present safety and efficacy results for the cohort of pts with aRCC of any histology and KPS 50%–60% from CheckMate 920 (NCT02982954). Methods: Pts with previously untreated advanced/metastatic RCC and KPS 50%–60% received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by 480 mg NIVO Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 25 treated pts with KPS 50%–60%, 76% were men; median age was 67 years (range, 34–81). IMDC risk was favorable in 0%, intermediate in 32%, and poor in 68% of pts; 84% had clear cell and 16% had non-clear cell RCC histology. With a minimum follow-up of 25 months, median duration of therapy (95% CI) was 2.3 months (2.1–7.7) for NIVO and 2.1 months (2.1–2.1) for IPI. The median number of doses (range) received was 4 (1–27) for NIVO and 4 (1–4) for IPI; 76% of pts received ≥ 4 NIVO doses and 68% received all 4 IPI doses. The only grade 3–4 imAEs by category were hepatitis (4.0%) and adrenal insufficiency (4.0%). No grade 5 imAEs occurred. Overall, 4 (16%) pts discontinued due to any-grade adverse events (n = 1 each for elevated AST, malignant neoplasm progression, back pain, and acetabulum fracture). Of 18 evaluable pts, ORR was 33.3% (95% CI, 13.3–59.0); no pts had a complete response and 6 had partial response. Median time to objective response was 4.5 months (range, 2.5–24.7). Median duration of objective response was 20.6 months (range, 0.03+–24.2+). Median PFS was 4.6 months (95% CI, 2.5–14.8). Median OS was 15.6 months (95% CI, 5.3–25.1). Conclusions: NIVO+IPI demonstrated an acceptable safety profile and promising antitumor activity in pts with previously untreated aRCC and KPS 50%–60%. The combination was tolerated at a dose intensity similar to that observed in clinical trials conducted in pts with higher KPS (≥ 70%). These data support the value of NIVO+IPI in pts who may not be considered ideal candidates for this therapy and consequently may have limited treatment options. Clinical trial information: NCT02982954 .

Multi-center, single arm phase II study of the dual mTORC1/mTORC2 inhibitor vistusertib for patients with recurrent or progressive grade II-III meningiomas.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2024-2024
Author(s):  
Scott Randall Plotkin ◽  
Priya Kumthekar ◽  
Patrick Y. Wen ◽  
Frederick G. Barker ◽  
Anat Stemmer-Rachamimov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Duration Of Treatment ◽  
Cross Sectional ◽  
Pathway Activation ◽  
Grade Ii ◽  
Correlative Studies

2024 Background: Grade II/III meningiomas represent about 20% of tumors and have increased rates of recurrence with no approved medical therapies. Historically, the progression-free survival at 6 months (PFS-6) for these tumors is 25%. The Response Assessment in Neuro-Oncology (RANO) group identified a PFS-6 rate of > 35% to be of interest for trials of grade II/III meningioma. Methods : NF2 gene inactivation occurs in the majority of meningiomas and is associated with mTORC1 activation. Human studies of everolimus for neurofibromatosis 2 patients documented growth arrest in only a minority of tumors. Based on our studies showing mTORC2/SGK1 pathway activation in NF2-deficient meningiomas and the known paradoxical activation of the mTORC2/AKT pathway in meningiomas, we hypothesized that dual inhibition of mTORC1/2 would be superior in meningiomas. Treatment of primary meningioma cells with vistusertib led to decreased cell proliferation and showed greater efficacy than rapamycin, regardless of NF2 expression. We studied the effect of vistusertib in patients with progressive or recurrent grade II/III meningiomas (NCT03071874). Vistusertib was administered orally at 125mg twice daily on two consecutive days each week. MRIs were obtained every 2 cycles (1 cycle = 28 days). Tumor size was defined as the largest cross-sectional area. Progression was defined as ≥25% increase in the sum of products of all measurable lesions over smallest sum observed. The primary endpoint was PFS-6. Secondary endpoints included toxicity, radiographic response, and correlative studies including immunohistochemistry for mTORC1/2 pathway activation and genetic biomarkers. Results: Twenty-eight patients (13 female), with a median age of 58 years (range, 32 to 77 years), were enrolled in this multicenter study. The median Karnofsky performance status was 80. Twenty-five patients have been followed to six months or to tumor progression. The median duration of treatment was 6.5 month (range, 1-18 months). Four patients chose to discontinue treatment, 1 withdrew to intercurrent illness, and 1 was withdrawn due to non-compliance. PFS-6 is 51.5% (CI, 29.3% - 70.0%). Adverse events at least possibly related to vistusertib with frequency > 10% include nausea (54%); fatigue (36%); hypophosphatemia (29%); diarrhea, anorexia, dry mouth, and hypertriglyceridemia (all 14%); hypertension, vomiting, increased ALT, constipation, and weight loss (all 11%). Conclusions: Vistusertib treatment was associated with a PFS-6 rate that exceeds the RANO target of 35% for recurrent high-grade meningioma. The follow-up data continue to mature. Adverse events were tolerable in this patient population. Correlative studies to identify biological factors that correlate with response are under way. These data support the initiation of larger randomized studies of vistusertib in this setting. Clinical trial information: NCT03071874.

scholarly journals Clinicopathologic Features and Early Surgical Outcome of Astrocytomas in Eldoret, Kenya

2018 ◽  
Vol 09 (03) ◽  
pp. 363-369
Author(s):  
Clifford C. Mwita ◽  
Florentius Koech ◽  
Titus Sisenda ◽  
Kirtika Patel ◽  
Benson Macharia ◽  
...  
Keyword(s):  
Functional Status ◽  
Tumor Size ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Neurological Deficits ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Short Term ◽  
Duration Of Illness ◽  
Mri Score

ABSTRACT Background: Astrocytomas are primary central nervous system tumors arising from astrocytes and accounting for up to 37.8% of all brain tumors seen in hospital-based studies from Africa. Despite being common, their patterns and short-term outcomes remain poorly studied in Kenya. Materials and Methods: A prospective, descriptive study involving consecutive patients with a histological diagnosis of astrocytoma seen in three hospitals located in Eldoret, Kenya. Clinicopathologic characteristics and outcomes were recorded and patients followed up for 12 weeks. Results: Thirty-one patients were recruited over a 1-year period. Majority of them were female (51.6%). Headache (83.9%) and focal neurological deficits (64.5%) were the most common presenting features. Among patients with high-grade tumors, mean duration of illness was 106.03 ± 162.16 days, median functional status was Karnofsky performance status (KPS) score 50, mean tumor size was 110.22 ± 46.16 cm3, and median magnetic resonance imaging (MRI) score was 17. Among patients with low-grade astrocytomas, mean duration of illness was 213.03 ± 344.93 days, median functional status was KPS score 40, mean tumor size was 53.49 ± 54.96 cm3 and median MRI score was 9. Glioblastoma multiforme (GBM) (71%) and diffuse astrocytoma (22.6%) were the predominant histological subtypes. The median Ki-67 proliferative index was 6% for pilocytic astrocytoma, 1.6% for diffuse astrocytoma, and 60% for GBM. Systemic and regional surgical complications occurred in 6.5% and 38.7% of patients, respectively. In-hospital mortality was 19.4% and increased to 25.8% at 12 weeks. The KPS score at discharge was 50 and improved to 60 at 12 weeks. Only 9.7% of patients had acceptable functional status at 12 weeks follow-up. Conclusions: In this locality, headache, focal neurological deficits, and reduced functional status are the most common presenting features of astrocytomas while GBM is the most common histological subtype. Tumors are highly proliferative and in the short-term, both surgical and functional outcome are suboptimal.

Postoperative ischemic changes following brain metastasis resection as measured by diffusion-weighted magnetic resonance imaging

2013 ◽  
Vol 119 (6) ◽  
pp. 1395-1400 ◽  
Author(s):  
Jens Gempt ◽  
Julia Gerhardt ◽  
Vivien Toth ◽  
Stefanie Hüttinger ◽  
Yu-Mi Ryang ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Neurological Deficit ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Neurological Status ◽  
Neurological Deficits ◽  
Brain Irradiation ◽  
Diffusion Weighted ◽  
The Mean

Object Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits. Methods Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded. Results One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003). Conclusions This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.

scholarly journals An Overview of Spinal Injuries due to Dive or Fall into Shallow Water: Our Long-Term, Double-Center Experience from the Aegean Coast

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Murat Yılmaz ◽  
Ersin Ikizoglu ◽  
Mert Arslan ◽  
Erkin Ozgiray ◽  
Kadri Emre Calıskan ◽  
...  
Keyword(s):  
Shallow Water ◽  
Clinical Features ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Target Population ◽  
Spinal Injuries ◽  
Neurological Deficits ◽  
Spine Injury ◽  
Cervical Injury ◽  
Therapeutic Outcomes

Purpose. We aimed to evaluate the demographic and clinical features of patients with cervical spinal injuries secondary to shallow-water diving and share our therapeutic outcomes. Methods. A retrospective study was carried out using data extracted from the medical files of 39 patients (3 females and 36 males) who were treated surgically (n = 29) or conservatively (n = 10). Demographics, clinical features, operative data, American Spine Injury Association (ASIA) impairment scales, and Karnofsky Performance Status (KPS) results were noted. Results. The average age of our series (n = 39) was 31.59 ± 14.80 (range, 14 to 92) years. The vast majority of patients (n = 34, 87.2%) presented with isolated cervical trauma. At initial admission, neurological deficits were diagnosed in 22 (56.4%) patients. A single-level cervical involvement was noted in 18 (46.2%) patients, while 21 cases (53.8%) displayed injury involving multiple levels. The levels of cervical injury were C5 (n = 16, 41%), C6 (n = 11, 28.2%), C7 (n = 6, 15.4%), C1 (n = 5, 12.8%), and C4 (n = 1, 2.6%). A total of 22 patients had neurological deficits at admission. Surgery was performed using anterior (n = 21, 72.4%), posterior (n = 7, 24.1%), and combined anterior and posterior (n = 1, 3.4%) routes. Nine patients (23.1%) exhibited improvement in their neurological deficits. There were significant improvements in both the ASIA impairment scale and KPS results after treatment. Conclusion. Our data indicated that dive- or fall-related cervical spinal injuries are associated with profound morbidity. Reinforcement of primary prevention, identification of target population, and increased awareness on this topic are the key steps to minimize the frequency and severity of complications and to optimize therapeutic outcomes.

Phase 3 KEYNOTE-426 trial: Pembrolizumab (pembro) plus axitinib versus sunitinib alone in treatment-naive advanced/metastatic renal cell carcinoma (mRCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4597-TPS4597 ◽  
Author(s):  
Brian I. Rini ◽  
Thomas Powles ◽  
Mei Chen ◽  
Markus Puhlmann ◽  
Michael B. Atkins
Keyword(s):  
Adverse Events ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Risk Category ◽  
Antiangiogenic Agents ◽  
Phase 3 ◽  
End Points ◽  
Patient Reported ◽  
Treatment Naïve

TPS4597 Background: Antiangiogenic agents, including sunitinib and axitinib, have shown clinically significant efficacy in patients (pts) with mRCC. Results from a phase 1b study in 52 pts suggest first-line pembro, an anti–programmed death 1 antibody, in combination with axitinib, has substantial antitumor activity in mRCC (objective response rate [ORR], 71%) and manageable toxicity. The phase 3, multicenter, open-label, randomized KEYNOTE-426 study (NCT02853331) is designed to evaluate the efficacy and safety of pembro plus axitinib versus sunitinib alone in pts with treatment-naive mRCC. Methods: Key eligibility criteria include age ≥18 years, histologically confirmed mRCC with clear cell component (with or without sarcomatoid features), measurable disease (RECIST v1.1, investigator review), no prior systemic therapy for advanced disease, Karnofsky performance status ≥70%, and provision of a tumor sample for biomarker analyses. Before randomization, pts will be stratified by International Metastatic RCC Database Consortium risk category and geographic region. 840 pts will be randomly assigned 1:1 to receive pembro 200 mg every 3 wk + axitinib 5 mg twice daily or sunitinib 50 mg once daily for 4 wk followed by 2 wk off. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or withdrawal of consent. Pts in the pembro arm may receive up to 35 doses of pembro, after which axitinib-only treatment may continue. Imaging will be performed at wk 12, then every 6 wk for the first year, and every 12 wk thereafter. Bone scans will be performed at baseline, and if positive, repeated at wk 18, 30, 42, and 54, and every 24 wk thereafter. AEs will be monitored throughout and graded per National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Primary end points are to compare progression-free survival (RECIST v1.1, central review) and overall survival between treatment arms. Secondary end points include the comparison of ORR, duration of response, disease control rate, safety, and patient-reported outcomes between arms. Enrollment is ongoing. Clinical trial information: NCT02853331.

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