Efficacy, Outcome, and Safety of Elderly Patients with Glioblastoma in the 5-ALA Era: Single Center Experience of More Than 10 Years

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm3), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients.

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5-Aminolevulinic Acid guided resection improves the overall survival of patients with Glioblastoma - A comparative cohort study of 343 patients

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab047 ◽

2021 ◽

Author(s):

Asfand Baig Mirza ◽

Ioannis Christodoulides ◽

Jose Pedro Lavrador ◽

Anastasios Giamouriadis ◽

Amisha Vastani ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Neurological Deficit ◽

Aminolevulinic Acid ◽

Performance Status ◽

Progression Free Survival ◽

Extent Of Resection ◽

Motor Deficits ◽

Focal Neurological Deficit ◽

Guided Surgery

Abstract Background 5-Aminolevulic Acid guided surgery (5-ALA-GS) improves the extent of resection and progression free survival in patients with glioblastoma multiforme (GBM). Methods Single-center retrospective cohort study of adult patients with GBM who had surgical resection between 2013 and 2019, 5-ALA guided versus a non 5-ALA cohort. Primary outcome was the overall survival (OS). Secondary outcomes were extent of resection (EoR), performance status (PS), and new focal neurological deficit. Results 343 patients were included: 253 patients in 5-ALA-GS Group and 90 patients in the non-5-ALA-GS Group. The OS (17.47 versus 10.63 months, p<0.0001), post-operative PS (p<0.0001), PS at 6 months (p=0.002), new focal neurological deficit (23.3% versus 44.9%, p<0.0001) and radiological EoR (gross total resection (GTR) - 47.4% versus 22.9%, p< 0.0001) were significantly better in the 5-ALA-GS Group compared to non-5-ALA-GS Group. In multivariate analysis, use of 5-ALA (p=0.003) and MGMT promoter methylation (p=0.001) were significantly related with a better OS. In patients with radiological GTR, OS was also significantly better (p<0.0001) in the 5-ALA-GS Group compared to the non-5-ALA-GS Group. Conclusions 5-ALA guided surgery is associated with a significant improvement in the OS, PS after surgery and at six months, larger EoR, and fewer new motor deficits in patients with GBM.

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Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study

Journal of Neurosurgery ◽

10.3171/2019.6.jns191531 ◽

2020 ◽

Vol 133 (5) ◽

pp. 1324-1331 ◽

Cited By ~ 2

Author(s):

Rasmus W. Hansen ◽

Christian B. Pedersen ◽

Bo Halle ◽

Anders R. Korshoej ◽

Mette K. Schulz ◽

...

Keyword(s):

Overall Survival ◽

Tumor Volume ◽

Fluorescent Dyes ◽

Aminolevulinic Acid ◽

Progression Free Survival ◽

Extent Of Resection ◽

Sodium Fluorescein ◽

High Grade ◽

Free Survival ◽

High Grade Gliomas

OBJECTIVEMaximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.METHODSA total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.RESULTSOne hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).CONCLUSIONSFluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

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Extent of resection of peritumoral diffusion tensor imaging–detected abnormality as a predictor of survival in adult glioblastoma patients

Journal of Neurosurgery ◽

10.3171/2016.1.jns152153 ◽

2017 ◽

Vol 126 (1) ◽

pp. 234-241 ◽

Cited By ~ 32

Author(s):

Jiun-Lin Yan ◽

Anouk van der Hoorn ◽

Timothy J. Larkin ◽

Natalie R. Boonzaier ◽

Tomasz Matys ◽

...

Keyword(s):

Overall Survival ◽

Diffusion Tensor Imaging ◽

Cox Regression ◽

Aminolevulinic Acid ◽

Diffusion Tensor ◽

Methylation Status ◽

Progression Free Survival ◽

Extent Of Resection ◽

Extensive Resection ◽

Free Survival

OBJECTIVE Diffusion tensor imaging (DTI) has been shown to detect tumor invasion in glioblastoma patients and has been applied in surgical planning. However, the clinical value of the extent of resection based on DTI is unclear. Therefore, the correlation between the extent of resection of DTI abnormalities and patients' outcome was retrospectively reviewed. METHODS A review was conducted of 31 patients with newly diagnosed supratentorial glioblastoma who underwent standard 5-aminolevulinic acid–aided surgery with the aim of maximal resection of the enhancing tumor component. All patients underwent presurgical MRI, including volumetric postcontrast T1-weighted imaging, DTI, and FLAIR. Postsurgical anatomical MR images were obtained within 72 hours of resection. The diffusion tensor was split into an isotropic (p) and anisotropic (q) component. The extent of resection was measured for the abnormal area on the p, q, FLAIR, and postcontrast T1-weighted images. Data were analyzed in relation to patients' outcome using univariate and multivariate Cox regression models controlling for possible confounding factors including age, O6-methylguanine-DNA-methyltrans-ferase methylation status, and isocitrate dehydrogenase–1 mutation. RESULTS Complete resection of the enhanced tumor shown on the postcontrast T1-weighted images was achieved in 24 of 31 patients (77%). The mean extent of resection of the abnormal p, q, and FLAIR areas was 57%, 83%, and 59%, respectively. Increased resection of the abnormal p and q areas correlated positively with progression-free survival (p = 0.009 and p = 0.006, respectively). Additionally, a larger, residual, abnormal q volume predicted significantly shorter time to progression (p = 0.008). More extensive resection of the abnormal q and contrast-enhanced area improved overall survival (p = 0.041 and 0.050, respectively). CONCLUSIONS Longer progression-free survival and overall survival were seen in glioblastoma patients in whom more DTI-documented abnormality was resected, which was previously shown to represent infiltrative tumor. This highlights the potential usefulness and the importance of an extended resection based on DTI-derived maps.

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Outcome of total arterial versus conventional myocardial revascularization in the elderly: a single center experience

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0034-1367217 ◽

2014 ◽

Vol 62 (S 01) ◽

Author(s):

A. Haneya ◽

J. Jussli-Melchers ◽

S. Eckmann ◽

R. Berndt ◽

A. Thiem ◽

...

Keyword(s):

Myocardial Revascularization ◽

The Elderly ◽

Single Center ◽

Single Center Experience

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Neuroblastoma with intracerebral metastases and the need for neurosurgery: a single-center experience

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.7.peds19143 ◽

2020 ◽

Vol 25 (1) ◽

pp. 51-56

Author(s):

Steffen Fleck ◽

Sascha Marx ◽

Clara Bobak ◽

Victoria Richter ◽

Stephan Nowak ◽

...

Keyword(s):

Pediatric Patients ◽

Neurosurgical Procedures ◽

Normal Brain ◽

Indications For Surgery ◽

Single Center ◽

Neurosurgical Procedure ◽

Oncological Treatment ◽

Single Center Experience ◽

Stage 4 ◽

Neurosurgical Treatment

OBJECTIVEIntracerebral metastases in neuroblastoma patients are rare, and information about the indication for and the outcome of neurosurgical procedures in this setting is scarce in the literature. The authors’ aim in the present study was to report a single-center experience with the neurosurgical treatment of intracerebral metastases in neuroblastoma.METHODSThis study is a retrospective single-center analysis of all neurosurgical strategies used in the treatment of intracerebral metastases in neuroblastoma patients.RESULTSBetween 2009 and 2017, 237 pediatric patients (94 girls, 143 boys) with a mean age of 39 months at diagnosis were treated for neuroblastoma. Five (2.1%) of the 237 patients had a neurosurgical procedure for intracerebral metastases. The metastases occurred a mean of 46 months after initial diagnosis. All of these patients had neuroblastoma stage 4. Indications for surgery were recurrent metastases after initial successful oncological treatment or progression of the metastasis under oncological treatment as well as deterioration of neurological function. Intraoperatively, the tumor usually had a distinguishable dissection plane but was infiltrative to adjacent nerves in some spots. Mean overall survival after the neurosurgical procedure was 22 months. Furthermore, in another 3 patients, a neurosurgical procedure was done for an intracranial but extracerebral metastasis.CONCLUSIONSNeurosurgical procedures for intracerebral metastases in neuroblastoma patients are rare and were performed in 2.1% of patients in the present study. Intracerebral metastases occurred during disease progression, and the prognosis after surgery was very limited. The main indications for surgery were rapid neurological deterioration or recurrence of the metastasis after initial successful oncological treatment. Intraoperatively, the metastases usually had a distinguishable dissection plane from the normal brain tissue.

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Perspectives on the Therapeutic Benefits of Arginine Supplementation in Cancer Treatment

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190116121451 ◽

2019 ◽

Vol 19 (7) ◽

pp. 913-920

Author(s):

Fabiani L. R. Beal ◽

Pedro R. Beal ◽

Juliana R. Beal ◽

Natan Carvalho-Neves ◽

Octávio L. Franco ◽

...

Keyword(s):

Amino Acid ◽

Side Effects ◽

Cancer Treatment ◽

Treatment Strategies ◽

Endothelial Permeability ◽

The Elderly ◽

Therapeutic Benefits ◽

Cell Growth And Differentiation ◽

The Cost ◽

Arginine Supplementation

Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. Objective: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. Results: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. Conclusion: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.

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Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs

Pharmaceutics ◽

10.3390/pharmaceutics13040508 ◽

2021 ◽

Vol 13 (4) ◽

pp. 508

Author(s):

Sara Silva ◽

António J. Almeida ◽

Nuno Vale

Keyword(s):

Side Effects ◽

Dopaminergic Neurons ◽

Lewy Bodies ◽

Pharmacokinetic Profile ◽

The Elderly ◽

Motor Symptoms ◽

Administration Routes ◽

Pharmaceutical Therapy ◽

Drug Pharmacokinetic ◽

The Brain

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

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Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models

BMC Gastroenterology ◽

10.1186/s12876-021-01815-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yongfei He ◽

Tianyi Liang ◽

Shutian Mo ◽

Zijun Chen ◽

Shuqi Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Cancer ◽

Elderly Patients ◽

Surgical Resection ◽

Influencing Factors ◽

The Elderly ◽

Primary Hepatocellular Carcinoma ◽

Surgical Timing ◽

Duration Of Surgery

Abstract Background The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. Methods A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. Results A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. Conclusions We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

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Venous Thromboembolism Anticoagulation Prophylaxis Timing in Patients Undergoing Craniotomy for Tumor

Neurosurgery Open ◽

10.1093/neuopn/okaa018 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Hanna Algattas ◽

Spencer E Talentino ◽

Bradley Eichar ◽

Abraham A Williams ◽

Joseph M Murphy ◽

...

Keyword(s):

Venous Thromboembolism ◽

Clinical Judgment ◽

Tumor Resection ◽

The Elderly ◽

Extent Of Resection ◽

Subtotal Resection ◽

Hemorrhagic Complication ◽

Increased Risk ◽

Hemorrhagic Complications ◽

Prophylactic Anticoagulation

ABSTRACT BACKGROUND Prophylactic anticoagulation helps prevent postoperative venous thromboembolism (VTE) and time to initiation postcraniotomy has relied on clinical judgment and practice patterns. OBJECTIVE To compare risks of postoperative VTE and hemorrhage among patients undergoing tumor resection with initiation of prophylactic anticoagulation on postoperative day 1 (POD1) vs POD2. METHODS Adult patients undergoing craniotomy for tumor between 2008 and 2018 were retrospectively reviewed. Outcomes were recorded from the Electronic medical record (EMR) including deep vein thrombosis (DVT), pulmonary embolism (PE), and hemorrhage. RESULTS Of a total of 1168 patients undergoing craniotomy, 225 initiated anticoagulation on POD1 and 389 initiated on POD2. Of the 171 glioblastoma (GBM) cases, 64 initiated on POD1 and 107 on POD2. There were 9 DVTs (1.5%), 1 PE (0.20%), overall VTE rate of 1.6%, and 7 hemorrhagic complications (1.10%), 4 being clinically significant. The GBM cohort contained 4 DVTs (2.3%) and 3 hemorrhagic complications (1.80%). There was no increased risk of VTE or hemorrhage with anticoagulation initiated on POD2 compared to POD1 in either cohort. Multivariate analysis in both cohorts did not reveal a significant association between DVT, PE, or hemorrhagic complications with age, body mass index, GBM pathology, or extent of resection. Interestingly, glioma patients older than 70 with subtotal resection had a higher likelihood of suffering intracranial hemorrhage when anticoagulation was started on POD1 (odds ratio 12.98). CONCLUSION Risk of VTE or hemorrhagic complication did not significantly differ with prophylactic anticoagulation started on POD1 vs POD2. Early anticoagulation may certainly be considered in high risk cases; however, 1 group where risk may outweigh benefit is the elderly glioma population receiving a subtotal resection.

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