Symptom Burden in Glioblastoma: A Prospective Pilot Study from Diagnosis to First Progression.

INTRODUCTION: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. METHODS: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. RESULTS: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. DISCUSSION/CONCLUSION: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

Predictors for delayed awakening in adult glioma patients receiving awake craniotomy under monitored anesthesia care.

PURPOSE: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown. METHODS: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles. RESULTS: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate. CONCLUSION: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate.

Surgical Complexity and Complications: The Need for a Common Language.

BACKGROUND: Quality measurement and outcome assessment have recently caught an attention of the neurosurgical community, but lack of standardized definitions and methodology significantly complicates these tasks. OBJECTIVE: To identify a uniform definition of neurosurgical complications, to classify them according to etiology, and to evaluate them comprehensively in cases of intracranial tumor removal in order to establish a new, easy, and practical grading system capable of predicting the risk of postoperative clinical worsening of the patient condition. METHODS: A retrospective analysis was conducted on all elective surgeries directed at removal of intracranial tumor in the authors' institution during 2-year study period. All sociodemographic, clinical, and surgical factors were extracted from prospectively compiled comprehensive patient registry. Data on all complications, defined as any deviation from the ideal postoperative course occurring within 30 days of the procedure, were collected with consideration of the required treatment and etiology. A logistic regression model was created for identification of independent factors associated with worsening of the Karnofsky Performance Scale (KPS) score at discharge after surgery in comparison with preoperative period. For each identified statistically significant independent predictor of the postoperative worsening, corresponding score was defined, and grading system, subsequently named Milan Complexity Scale (MCS), was formed. RESULTS: Overall, 746 cases of surgeries for removal of intracranial tumor were analyzed. Postoperative complications of any kind were observed in 311 patients (41.7%). In 223 cases (29.9%), worsening of the KPS score at the time of discharge in comparison with preoperative period was noted. It was independently associated with 5 predictive factors-major brain vessel manipulation, surgery in the posterior fossa, cranial nerve manipulation, surgery in the eloquent area, tumor size >4 cm-which comprised MCS with a range of the total score from 0 to 8 (higher score indicates more complex clinical situations). Patients who demonstrated KPS worsening after surgery had significantly higher total MCS scores in comparison with individuals whose clinical status at discharge was improved or unchanged (3.24 ± 1.55 versus 1.47 ± 1.58; P < 0.001). CONCLUSION: It is reasonable to define neurosurgical complication as any deviation from the ideal postoperative course occurring within 30 days of the procedure. Suggested MCS allows for standardized assessment of surgical complexity before intervention and for estimating the risk of clinical worsening after removal of intracranial tumor. Collection of data on surgical complexity, occurrence of complications, and postoperative outcomes, using standardized prospectively maintained comprehensive patient registries seems very important for quality measurement and should be attained in all neurosurgical centers.

Functional status and survival in patients ≥85 years of age who have keratinocyte carcinoma: A retrospective cohort study.

BACKGROUND: Functional status assessment may help estimate which patients ≥85 years of age will benefit from surgical treatment for keratinocyte carcinoma (KC), but predictive value for short-term survival in this population has not been determined. OBJECTIVE: We sought to assess the predictive value of functional status for short-term survival in patients ≥85 years of age who have KC. METHODS: This was a retrospective cohort review of 238 patients ≥85 years of age who presented for the management of KC between 2010 and 2015. Functional status was assessed with the Karnofsky Performance Scale (KPS) and Katz Activities of Daily Living (ADL) index. Overall survival was determined. RESULTS: Lower functional status scores of KPS ≤40 and Katz ADL ≤4 were associated with 37% and 53% survival at 2 years, respectively. LIMITATIONS: Retrospective design and single-center study. CONCLUSION: In this study, KPS and Katz ADL predicted short-term survival. Patients with low functional status scores had significantly decreased survival at 2 years, with double the death rate of patients with high functional status. Functional status should be considered during shared decision-making for elderly individuals who are seeking treatment for KC.

Resection of meningiomas in octogenarians: a comparison with a younger geriatric population.

OBJECTIVE: Intracranial meningiomas (ICMs) may be diagnosed in octogenarians. Since the lesions are rarely life-threatening, surgery is a questionable choice in this age group. The authors' aim in this study was to analyze factors associated with the extent of resection (EOR), overall survival (OS), and postoperative complications in octogenarians undergoing ICM surgery, by using a cohort of septuagenarians as a reference. METHODS: All patients ≥ 70 years of age who underwent surgery at Oslo University Hospital for an ICM between 1990 and 2010 were included in this study. Data on these cases were retrospectively (1990-2002) and prospectively (2003-2010) acquired from a databank belonging to Oslo University Hospital. All related preoperative imaging studies or reports (earlier cases) were reviewed to confirm tumor location, the presence of bone invasion, and the postoperative EOR. RESULTS: In this study, 49 octogenarians (29 females [59.2%], mean age 83.3 ± 2.5 years) were compared with 272 septuagenarians (173 females [63.6%], mean age 74.3 ± 2.7 years). Forty octogenarians (81.6%) and 217 septuagenarians (79.8%) underwent gross-total resection. Simpson grade IV resection was achieved in 9 octogenarians (18.4%) and 4 septuagenarians (1.4%), while Simpson grade V resection was obtained in 4 septuagenarians (1.4%). Postoperative complications were similar in both groups, and 4 octogenarians (8.2%) and 11 septuagenarians (4.1%) died within 30 days after surgery (p = 0.25). No octogenarian underwent adjuvant radiotherapy. The OS was 4.2 ± 2.8 years in the octogenarians and 5.8 ± 4.4 years in the septuagenarians (p < 0.001). Female sex (OR 0.36, 95% CI 0.14-0.93; p = 0.03) and a preoperative Karnofsky Performance Scale score ≥ 70 (OR 0.27, 95% CI 0.10-0.72; p = 0.009) were correlated to the OS. CONCLUSIONS: Octogenarians undergoing surgery for ICMs had an overall reduced OS compared to septuagenarians. However, the clinical relevance of this difference in OS is debatable and has to be put in perspective with expected survival without surgery. Data on symptoms upon admission, EOR, invasive tumor features, and postoperative complications in octogenarians are similar to those observed in septuagenarians. Therefore, the decision concerning whether surgery should be performed must be based on a case-by-case discussion, and surgery should not be immediately dismissed when it comes to ICMs in octogenarians.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Tractography and the connectome in neurosurgical treatment of gliomas: the premise, the progress, and the potential.

The ability of diffusion tensor MRI to detect the preferential diffusion of water in cerebral white matter tracts enables neurosurgeons to noninvasively visualize the relationship of lesions to functional neural pathways. Although viewed as a research tool in its infancy, diffusion tractography has evolved into a neurosurgical tool with applications in glioma surgery that are enhanced by evolutions in crossing fiber visualization, edema correction, and automated tract identification. In this paper the current literature supporting the use of tractography in brain tumor surgery is summarized, highlighting important clinical studies on the application of diffusion tensor imaging (DTI) for preoperative planning of glioma resection, and risk assessment to analyze postoperative outcomes. The key methods of tractography in current practice and crucial white matter fiber bundles are summarized. After a review of the physical basis of DTI and post-DTI tractography, the authors discuss the methodologies with which to adapt DT image processing for surgical planning, as well as the potential of connectomic imaging to facilitate a network approach to oncofunctional optimization in glioma surgery.

miR-145 is a potential biomarker for predicting clinical outcome in glioblastomas.

miR-145 has been found to be significantly downregulated in gliomas, and overexpression of miR-145 increases glioma cell apoptosis and enhances chemosensitivity or herpes simplex virus thymidine kinase gene therapy. However, the correlation between miR-145 and the clinical prognosis of glioblastomas has never been explored. In this study, a retrospective study was conducted in 86 cases of patients with glioblastoma after neurosurgery combined with chemoradiotherapy, and 36 cases with traumatic brain injury. Our results showed that miR-145 was significantly lower in glioblastoma tissues than that in normal brain tissue (P < 0.05). Furthermore, miR-145 was lower in patients with lower Karnofsky Performance Scale (KPS) scores than in patients with higher KPS scores ( P < 0.05). Cox Regression analysis showed that low miR-145 expression was associated with poor patient survival ( P < 0.05). These data suggested that patients with glioblastoma with lower miR-145 expression are prone to shorter overall survival.

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience.

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.

Gamma Knife radiosurgery for intracranial benign meningiomas: follow-up outcome in 130 patients.

OBJECTIVEThe authors retrospectively analyzed the follow-up data in 130 patients with intracranial benign meningiomas after Gamma Knife radiosurgery (GKRS), evaluated the tumor progression-free survival (PFS) rate and neurological function preservation rate, and determined the predictors by univariate and multivariate survival analysis.METHODSThis cohort of 130 patients with intracranial benign meningiomas underwent GKRS between May 2012 and May 2015 at the Second Hospital of Tianjin Medical University. The median age was 54.5 years (range 25-81 years), and women outnumbered men at a ratio of 4.65:1. All clinical and radiological data were obtained for analysis. No patient had undergone prior traditional radiotherapy or chemotherapy. The median tumor volume was 3.68 cm3 (range 0.23-45.78 cm3). A median margin dose of 12.0 Gy (range 10.0-16.0 Gy) was delivered to the tumor with a median isodose line of 50% (range 50%-60%).RESULTSDuring a median follow-up of 36.5 months (range 12-80 months), tumor volume regressed in 37 patients (28.5%), was unchanged in 86 patients (66.2%), and increased in 7 patients (5.4%). The actuarial tumor progression-free survival (PFS) rate was 98%, 94%, and 87% at 1, 3, and 5 years, respectively, after GKRS. Tumor recurred in 7 patients at a median follow-up of 32 months (range 12-56 months). Tumor volume ≥ 10 cm3 (p = 0.012, hazard ratio [HR] 8.25, 95% CI 1.60-42.65) and pre-GKRS Karnofsky Performance Scale score < 90 (p = 0.006, HR 9.31, 95% CI 1.88-46.22) were independent unfavorable predictors of PFS rate after GKRS. Of the 130 patients, 101 (77.7%) presented with one or more neurological symptoms or signs before GKRS. Neurological symptoms or signs improved in 40 (30.8%) patients, remained stable in 83 (63.8%), and deteriorated in 7 (5.4%) after GKRS. Two (1.5%) patients developed new cranial nerve (CN) deficit. Tumor volume ≥ 10 cm3 (p = 0.042, HR = 4.73, 95% CI 1.06-21.17) and pre-GKRS CN deficit (p = 0.045, HR = 4.35, 95% CI 0.84-22.48) were independent unfavorable predictors for improvement in neurological symptoms or signs. Six (4.6%) patients developed new or worsening peritumoral edema with a median follow-up of 4.5 months (range 2-7 months).CONCLUSIONSGKRS provided good local tumor control and high neurological function preservation in patients with intracranial benign meningiomas. Patients with tumor volume < 10 cm3, pre-GKRS Karnofsky Performance Scale score ≥ 90, and no pre-GKRS CN deficit (I-VIII) can benefit from stereotactic radiosurgery. It can be considered as the primary or adjuvant management of intracranial benign meningiomas.

Karnofsky Performance Scale validity and reliability of Turkish palliative cancer patients

Background/aim: Validated measures in palliative cancer patients are very important in the evaluation and management of the disease. The Karnofsky Performance Scale (KPS) has been used for many years to assess the performance status of cancer patients. The aim of this study is to determine the validity and reliability of the KPS in cancer patients receiving palliative care in Turkey. Materials and methods: Eighty patients with a cancer diagnosis who were admitted to Gaziosmanpasa University Medical Faculty Hospital Palliative Care Unit between 01.03.2016 and 01.03.2017 were included in the study. KPS, measurements from the Katz Activi-ties of Daily Living (ADL) scale, and Basic Activities of Daily Living (BADL) scale were recorded. The alpha coefficient (Cronbach) was calculated by using SPSS version 20.0. The P-value was accepted as P < 0.05 in the analysis of the data. Results: There was a positive and strong correlation between Katz ADL scale total score and KPS score (r = 0.895; P < 0.001). In ad-dition, there was a strong negative correlation between the total score of BADL scale and KPS score (r = ­0.894; P < 0.001). As for the reliability of the scale scores, Cronbach's alpha coefficient found to be 0.720. Conclusion: KPS is a reliable scale for Turkish cancer patients in palliative care settings.

Multivariate risk factor analysis and literature review of postoperative deterioration in Karnofsky Performance Scale score in elderly patients with skull base meningioma.

OBJECTIVE Elderly patients are particularly at risk for severe morbidity following surgery. Among the various risk factors, age and skull base location of meningioma are known to be poor prognostic factors in meningioma surgery. The authors conducted this study to analyze significant preoperative risk factors in elderly patients with skull base meningioma. METHODS A total of 265 elderly patients (≥ 65 years old) with meningioma were surgically treated at the authors' institute and affiliated hospitals between 2000 and 2016, and these cases were reviewed. Among them, 57 patients with skull base meningioma were evaluated. Among the various risk factors, the authors analyzed age, sex, Karnofsky Performance Scale (KPS) score, American Society of Anesthesiologists score, and tumor size, location, and pathology. Body mass index (BMI) and serum albumin were investigated as the frailty factors. The authors also reviewed 11 surgical studies of elderly patients ≥ 60 years old with meningioma. RESULTS The mean age was 72.4 ± 5.7 years, and 42 patients were female (73.6%). The mean size of meningioma was 36.6 ± 14.8 mm at the maximum diameter, and the mean follow-up period was 31.1 ± 31.5 months. (The continuous variables are expressed as the mean ± SD.) Histopathological investigation revealed a higher incidence (71.9%) of WHO Grade I. The rates of deterioration after surgery, at 3 months, and at 1 year were 33.3%, 37.3%, and 39.1%, respectively. Univariate analysis revealed location, preoperative KPS score, BMI level 2, and serum albumin level (p = 0.010, 0.017, 0.0012, and 0.0019, respectively) to be poor prognostic factors. Multivariate analysis revealed that location (p = 0.038) and BMI (p = 0.035) were risk factors for KPS score deterioration immediately after surgery. According to the 11 papers reviewed, the median rate (25th-75th percentile) of skull base-related location was 43.5% (39.6-47.75); for asymptomatic status the mean was 24%; and for mortality at 3 months and 1 year the medians were 6.3% (0.7-7.1) and 8% (4.8-9.4), respectively. CONCLUSION Careful preoperative assessment based on the frailty concept was essential for better outcome in elderly patients with skull base meningioma. The BMI is appropriate as a quantitative factor for measure of frailty, particularly in elderly individuals with skull base meningioma. Further prospective randomized controlled trials are necessary to validate frailty as a preoperative risk factor. Not only patient selection but also surgical timing was an important factor.

Safe maximal resection of primary cavernous sinus meningiomas via a minimal anterior and posterior combined transpetrosal approach.

OBJECTIVE Meningiomas arising from the cavernous sinus (CS) continue to be a significant technical challenge, and resection continues to carry a relatively higher risk of neurological morbidity in patients with these lesions because of the tumor's proximity to neurovascular structures. The authors report the surgical outcomes of 9 patients with primary CS meningiomas (CSMs) that were surgically treated using a minimal anterior and posterior combined (MAPC) transpetrosal approach, and they emphasize the usefulness of the approach. METHODS This retrospective study included 9 patients who underwent surgery for CSM treatment between 2015 and 2016 via the MAPC transpetrosal approach. Two patients were men and 7 were women, with a mean age of 58.5 years (39-72 years). Five patients (55.5%) had undergone previous treatment. The surgical technique consisted of a temporo-occipito-suboccipital craniotomy and exposure of the posterolateral part of the CS via the presigmoidal MAPC approach. After opening Meckel's cave and identifying the 3rd-5th cranial nerves in the prepontine cistern, Parkinson's triangle and supratrochlear triangles were opened. Finally, the tumor occupying the posterolateral part of the CS was removed. RESULTS All lesions were safely and maximally removed, with preservation of external ocular movements and preoperative Karnofsky Performance Scale scores. The mean extent of resection was 77.0% (range 58.7%-95.4%). Six patients underwent adjuvant therapy in the form of stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) during the follow-up period; none of these patients experienced recurrence. CONCLUSION The authors conclude that the MAPC transpetrosal approach could be superior to other approaches for CSMs, as it provides direct visual access to the posterolateral portion of the CS. In their experience, this approach is an alternative and better option for safe maximal resection of CSMs.

Setup presentation and clinical outcome analysis of treating highly language-eloquent gliomas via preoperative navigated transcranial magnetic stimulation and tractography.

OBJECTIVE Awake surgery combined with intraoperative direct electrical stimulation (DES) and intraoperative neuromonitoring (IONM) is considered the gold standard for the resection of highly language-eloquent brain tumors. Different modalities, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), are commonly added as adjuncts for preoperative language mapping but have been shown to have relevant limitations. Thus, this study presents a novel multimodal setup consisting of preoperative navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) as an adjunct to awake surgery. METHODS Sixty consecutive patients (63.3% men, mean age 47.6 ± 13.3 years) suffering from highly language-eloquent left-hemispheric low- or high-grade glioma underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by awake surgery for tumor resection. Both nTMS language mapping and DTI FT data were available for resection planning and intraoperative guidance. Clinical outcome parameters, including craniotomy size, extent of resection (EOR), language deficits at different time points, Karnofsky Performance Scale (KPS) score, duration of surgery, and inpatient stay, were assessed. RESULTS According to postoperative evaluation, 28.3% of patients showed tumor residuals, whereas new surgery-related permanent language deficits occurred in 8.3% of patients. KPS scores remained unchanged (median preoperative score 90, median follow-up score 90). CONCLUSIONS This is the first study to present a clinical outcome analysis of this very modern approach, which is increasingly applied in neurooncological centers worldwide. Although human language function is a highly complex and dynamic cortico-subcortical network, the presented approach offers excellent functional and oncological outcomes in patients undergoing surgery of lesions affecting this network.

Frequency of symptomatic vertebral body compression fractures requiring intervention following single-fraction stereotactic radiosurgery for spinal metastases.

OBJECTIVE The purpose of this study was to determine the rate of symptomatic vertebral body compression fractures (VCFs) requiring kyphoplasty or surgery in patients treated with 24-Gy single-fraction stereotactic radiosurgery (SRS). METHODS This retrospective analysis included all patients who had been treated with 24-Gy, single-fraction, image-guided intensity-modulated radiation therapy for histologically confirmed solid tumor metastases over an 8-year period (2005-2013) at Memorial Sloan Kettering Cancer Center. Charts and imaging studies were reviewed for post-SRS kyphoplasty or surgery for mechanical instability. A Spinal Instability Neoplastic Score (SINS) was calculated for each patient both at the time of SRS and at the time of intervention for VCF. RESULTS Three hundred twenty-three patients who had undergone single-fraction SRS between C-1 and L-5 were included in this analysis. The cumulative incidence of VCF 5 years after SRS was 7.2% (95% CI 4.1-10.2), whereas that of death following SRS at the same time point was 82.5% (95% CI 77.5-87.4). Twenty-six patients with 36 SRS-treated levels progressed to symptomatic VCF requiring treatment with kyphoplasty (6 patients), surgery (10 patients), or both (10 patients). The median time to symptomatic VCF was 13 months. Seven patients developed VCF at 11 levels adjacent to the SRS-treated level. Fractured levels had no evidence of tumor progression. The median SINS changed from 6.5 at SRS (interquartile range [IQR] 4.3-8.8) to 11.5 at stabilization (IQR 9-13). In patients without prior stabilization at the level of SRS, there was an association between the SINS and the time to fracture. CONCLUSIONS Five years after ablative single-fraction SRS to spinal lesions, the cumulative incidence of symptomatic VCF at the treated level without tumor recurrence was 7.2%. Higher SINSs at the time of SRS correlated with earlier fractures.

Quality of life after different surgical procedures for the treatment of spinal metastases: results of a single-center prospective case series.

OBJECTIVE The performance of surgery for spinal metastases is rapidly increasing. Different surgical procedures, ranging from stabilization alone to stabilization combined with corpectomy, are thereby performed for various indications. Little is known about the impact of these different procedures on patient quality of life (QOL), but this factor is crucial when discussing the various therapeutic options with patients and their families. Thus, the authors of this study investigated the effect of various surgical procedures for spinal metastases on patient QOL. METHODS The authors prospectively followed a cohort of 113 patients with spinal metastases who were referred to their clinic for surgical evaluation between July 2012 and July 2014. Quality of life was assessed using the EQ-5D at intake and at 3, 6, 9, and 12 months after treatment. RESULTS Nineteen patients were treated conservatively, 41 underwent decompressive surgery with or without stabilization, 47 underwent a piecemeal corpectomy procedure with stabilization and expandable cage reconstruction, and 6 had a stabilization procedure without decompression. Among all surgical patients, the mean EQ-5D score was significantly increased from 0.44 pretreatment to 0.59 at 3 months after treatment (p < 0.001). Mean EQ-5D scores at 1 year after surgery further increased to 0.84 following decompression with stabilization, 0.74 after corpectomy with stabilization, and 0.94 after stabilization without decompression. Frankel scores also improved after surgery. There were no significant differences in improvements in EQ-5D scores and Frankel grades among the different surgical procedures. In addition, mortality and complication rates were similar. CONCLUSIONS Quality of life can improve significantly after various extensive and less extensive surgical procedures in patients with spinal metastases. The relatively invasive corpectomy procedure, as compared with alternative less invasive techniques, does not negatively affect outcome.

Fluorescence-Guided versus Conventional Surgical Resection of High Grade Glioma: A Single-Centre, 7-Year, Comparative Effectiveness Study.

BACKGROUND: High grade gliomas (HGGs) are locally invasive brain tumours that carry a dismal prognosis. Although complete resection increases median survival, the difficulty in reliably demonstrating the tumour border intraoperatively is a norm. The Department of Neurosurgery, Hospital Sungai Buloh is the first public hospital in Malaysia to overcome this problem by adopting fluorescence-guided (FG) surgery using 5-aminolevulinic acid (5-ALA). METHODS: A total of 74 patients with histologically proven HGGs treated between January 2008 and December 2014, who fulfilled the inclusion criteria, were enrolled. Kaplan-Meier survival estimates and Cox proportional hazard regression were used. RESULTS: Significant longer survival time (months) was observed in the FG group compared with the conventional group (12 months versus 8 months, P < 0.020). Even without adjuvant therapy, HGG patients from FG group survived longer than those from the conventional group (8 months versus 3 months, P = 0.006). No significant differences were seen in postoperative Karnofsky performance scale (KPS) between the groups at 6 weeks and 6 months after surgery compared to pre-operative KPS. Cox proportional hazard regression identified four independent predictors of survival: KPS > 80 (P = 0.010), histology (P < 0.001), surgical method (P < 0.001) and adjuvant therapy (P < 0.001). CONCLUSION: This study showed a significant clinical benefit for HGG patients in terms of overall survival using FG surgery as it did not result in worsening of post-operative function outcome when compared with the conventional surgical method. We advocate a further multicentered, randomised controlled trial to support these findings before FG surgery can be implemented as a standard surgical adjunct in local practice for the benefit of HGG patients.

Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non-small cell lung cancer study.

PURPOSE: Although cancer cachexia is mainly characterized by persistent loss of body weight (BW), usually in response to a malignancy, the pathophysiology of cachexia remains unresolved. To elucidate the relationship between the loss of BW and other related clinical factors, we conducted a nationwide, multi-institutional, prospective, observational study in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Treatment-naïve stage IV NSCLC patients with an Eastern Cooperative Oncology Group performance status (PS) of 0-2 were eligible. BW, handgrip strength (HGS), quality of life (QOL), Karnofsky Performance Scale (KPS), biochemical parameters, and survival were evaluated at baseline and every 4 weeks for 1 year. The relationship between BW loss and other factors was examined by linear regression analysis. Estimated survival curves were drawn by the Kaplan-Meier method and applied by the log-rank test. Clinical factors associated with cancer cachexia were identified through principal component analysis. The generalized estimating equation approach was used to analyze the deterioration of QOL resulting from the progression of cachexia. RESULTS: A total of 406 patients were analyzed. BW loss was significantly associated with worsening of QOL, HGS, KPS, and biochemical parameters. The incidence of BW loss was observed throughout the study period. Overall survival was significantly shorter in patients as BW loss progressed. BW loss, decrease in HGS, anorexia, and fatigue were identified as core factors of cachexia that contributed to the deterioration of QOL. CONCLUSION: BW loss most likely deteriorated QOL and shortened survival in patients with advanced NSCLC and should be closely monitored.

Aggressive surgery based on an anatomical subclassification of craniopharyngiomas.

OBJECTIVE Craniopharyngiomas remain a particularly formidable challenge in the neurosurgical field. Because these lesions involve the hypothalamus and ophthalmological systems, their resection is associated with either higher rates of mortality and recurrence or a lower rate of radical resection. The authors report the outcomes of aggressive surgeries based on an anatomical subclassification of craniopharyngiomas. METHODS Clinical and ophthalmological examinations, imaging studies, endocrinological studies, neuropsychological function, and surgical complications in all patients who had undergone microsurgical resection for craniopharyngioma at Osaka City University hospital between January 2000 and December 2014 were retrospectively reviewed through the medical records. Radical resections were planned in all of the patients. To help choose the correct surgical approach, craniopharyngiomas were classified based on tumor origin. The 4 possible groups included the intrasellar type, prechiasmatic type, retrochiasmatic type, and intra-third ventricle type. A multistage surgery was planned in some cases. RESULTS Seventy-two cases of craniopharyngioma were resected. Thirty-two patients (44.4%) had undergone previous surgical procedures at other institutions. Thirty-five cases (48.6%) were classified as retrochiasmatic, 19 (26.4%) as prechiasmatic, 12 (16.7%) as intra-third ventricle, and 6 (8.3%) as intrasellar. In 26 cases (36.1%), multistage surgery was required to complete the radical resection. Overall, 41 cases involved an orbitozygomatic approach; 21, a transpetrosal approach; 21, an interhemispheric approach; and 14, a transsphenoidal approach. In 3 cases, other approaches were applied. Gross-total resection was achieved in 43 patients (59.7%), near-total resection in 28 (38.9%), and partial resection in only 1 patient (1.4%). The mean follow-up period after resection was 4.7 years. Tumor recurrence or regrowth occurred in 15 (20.8%) of the 72 patients, with 14 of the 15 cases successfully controlled after additional resections and stereotactic radiosurgery. However, 1 patient died of uncontrollable tumor progression, and 2 patients died of unrelated diseases during the follow-up. Overall, disease in 69 (95.8%) of 72 patients was well controlled at the last follow-up. CONCLUSIONS Aggressive tumor resection is the authors' treatment policy for craniopharyngioma. Using an anatomical subclassification of craniopharyngioma to choose the most appropriate surgical approach is helpful in achieving that goal of aggressive resection.

Management and outcome of recurrent adult craniopharyngiomas: an analysis of 42 cases with long-term follow-up.

OBJECTIVE The treatment of recurrent and residual craniopharyngiomas is challenging. In this study the authors describe their experience with these tumors and make recommendations on their management. METHODS The authors performed an observational study of adult patients (≥ 18 years) with recurrent or residual craniopharyngiomas that were managed at their tertiary center. Retrospective data were collected on demographics and clinical, imaging, and treatment characteristics from patients who had a minimum 2-year follow-up. Descriptive statistics were used and the data were analyzed. RESULTS There were 42 patients (27 male, 15 female) with a mean age of 46.3 ± 14.3 years. The average tumor size was 3.1 ± 1.1 cm. The average time to first recurrence was 3.6 ± 5.5 years (range 0.2-27 years). One in 5 patients (8/42) with residual/recurrent tumors did not require any active treatment. Of the 34 patients who underwent repeat treatment, 12 (35.3%) had surgery only (transcranial, endoscopic, or both), 9 (26.5%) underwent surgery followed by adjuvant radiation therapy (RT), and 13 (38.2%) received RT alone. Eighty-six percent (18/21) had a gross-total (n = 4) or near-total (n = 14) resection of the recurrent/residual tumors and had good local control at last follow-up. One of 5 patients (7/34) who underwent repeat treatment had further treatment for a second recurrence. The total duration of follow-up was 8.6 ± 7.1 years. The average Karnofsky Performance Scale score at last follow-up was 80 (range 40-90). There was 1 death. CONCLUSIONS Based on this experience and in the absence of guidelines, the authors recommend an individualized approach for the treatment of symptomatic or growing tumors. This study has shown that 1 in 5 patients does not require repeat treatment of their recurrent/residual disease and can be managed with a "scan and watch" approach. On the other hand, 1 in 5 patients who had repeat treatment for their recurrence in the form of surgery and/or radiation will require further additional treatment. More studies are needed to best characterize these patients and predict the natural history of this disease and response to treatment.