Glioblastomas multiforme (GBMs) have a dismal prognosis. The Stupp protocol has improved survival in patients with GBM; however, as in many prospective studies, only nonelderly patients with a favorable performance status were enrolled in that study. 11 Other published clinical trials and retrospective chart reviews often exclude both elderly patients (maximum age is typically 70–75 years) and those with low Karnofsky Performance Scale (KPS) scores (minimum is usually 60 or 70). 2 , 6 Studies that evaluate a broader range of ages and performance statuses
Editorial: Low Karnofsky Performance Scale score and glioblastoma multiforme
J. Bradley Elder and E. Antonio Chiocca
Multivariate risk factor analysis and literature review of postoperative deterioration in Karnofsky Performance Scale score in elderly patients with skull base meningioma
Manish Kolakshyapati, Fusao Ikawa, Masaru Abiko, Takafumi Mitsuhara, Yasuyuki Kinoshita, Masaaki Takeda, Kaoru Kurisu, and The Alumni Association Group of the Department of Neurosurgery at Hiroshima University
, and 1 at the orbital fossa. All cases were histopathologically confirmed as meningioma. Preoperative Risk Factors Risk factors for meningioma have been extensively studied, and these include patient-related, tumor-related, and treatment-related factors. Among the various risk factors, we analyzed age, sex, preoperative Karnofsky Performance Scale (KPS) score, ASA class, and tumor size, location, and pathological type as preoperative risk factors. The BMI and serum albumin were investigated as the frailty factors in elderly patients. Postoperative Outcome The
Treatment outcomes for patients with glioblastoma multiforme and a low Karnofsky Performance Scale score on presentation to a tertiary care institution
Ovidiu Marina, John H. Suh, Chandana A. Reddy, Gene H. Barnett, Michael A. Vogelbaum, David M. Peereboom, Glen H. J. Stevens, Heinrich Elinzano, and Samuel T. Chao
The object of this study was to determine the benefit of surgery, radiation, and chemotherapy for patients with glioblastoma multiforme (GBM) and a low Karnofsky Performance Scale (KPS) score.
The authors retrospectively evaluated the records of patients who underwent primary treatment for pathologically confirmed GBM and with a KPS score ≤ 50 on initial evaluation for radiation therapy at a tertiary care institution between 1977 and 2006. Seventy-four patients with a median age of 69 years (range 19–88 years) and a median KPS score of 50 (range 20–50) were retrospectively grouped into the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Classes IV (11 patients), V (15 patients), and VI (48 patients). Patients underwent biopsy (38 patients) or tumor resection (36 patients). Forty-seven patients received radiation. Nineteen patients also received chemotherapy (53% temozolomide), initiated concurrently (47%) or after radiotherapy.
The median survival overall was 2.3 months (range 0.2–48 months). Median survival stratified by RPA Classes IV, V, and VI was 6.6, 6.6, and 1.8 months, respectively (p < 0.001, log-rank test). Median survival for patients receiving radiation (5.2 months) was greater than that for patients who declined radiation (1.6 months, p < 0.001). Patients in RPA Class VI appeared to benefit from radiotherapy only when tumor resection was also performed. The median survival from treatment initiation was greater for patients receiving chemotherapy concomitantly with radiotherapy (9.8 months) as compared with radiotherapy alone (1.7 months, p = 0.002). Of 20 patients seen for follow-up in the clinic at a median of 48 days (range 24–196 days) following radiotherapy, 70% were noted to have an improvement in the KPS score of between 10 and 30 points from the baseline score. On multivariate analysis, only RPA class (p = 0.01), resection (HR = 0.37, p = 0.001), and radiation therapy (HR = 0.39, p = 0.02) were significant predictors of a decreased mortality rate.
Patients with a KPS score ≤ 50 appear to have increased survival and functional status following tumor resection and radiation. The extent of benefit from concomitant chemotherapy is unclear. Future studies may benefit from reporting that utilizes a prognostic classification system such as the RTOG RPA class, which has been shown to be effective at separating outcomes even in patients with low performance status. Patients with GBMs and low KPS scores need to be evaluated in prospective studies to identify the extent to which different therapies improve outcomes.
Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases
Jay Jagannathan, Chun-Po Yen, Dibyendu Kumar Ray, David Schlesinger, Rod J. Oskouian, Nader Pouratian, Mark E. Shaffrey, James Larner, and Jason P. Sheehan
. Karnofsky Performance Scale Scores At the last clinical follow-up evaluation, the mean KPS score for the overall group was 78 (median 80, range 40–100). At the last follow-up evaluation, patients who received radiosurgery alone had higher KPS scores (mean 82, median 90, range 70–100) than those who received radiosurgery and WBRT (mean 66, median 70, range 40–100; Table 3 ). Overall, however, this difference in KPS scores between groups was not statistically significant and may reflect the overall trend that patients who received WBRT tended to have higher intracranial
Accuracy of operating neurosurgeons' prediction of functional levels after intracranial tumor surgery
Lisa Millgård Sagberg, Christina Drewes, Asgeir S. Jakola, and Ole Solheim
results may lead to incorrect patient information and nonbeneficial management strategies. Thus, it is important to be aware of the reliability of the clinical judgment. In other clinical disciplines, a tendency toward overoptimism has been demonstrated, both for predicting life expectancy and for other surgical results. 5 , 11 , 12 , 17 In this prospective study, we aimed to assess the accuracy of the operating neurosurgeons' prediction of functional levels 30 days after intracranial tumor surgery by comparing expected and observed Karnofsky Performance Scale (KPS
Predicting functional impairment in brain tumor surgery: the Big Five and the Milan Complexity Scale
Paolo Ferroli, Morgan Broggi, Silvia Schiavolin, Francesco Acerbi, Valentina Bettamio, Dario Caldiroli, Alberto Cusin, Emanuele La Corte, Matilde Leonardi, Alberto Raggi, Marco Schiariti, Sergio Visintini, Angelo Franzini, and Giovanni Broggi
’s general health status. For tumors located in eloquent areas, extended neurophysiological monitoring and, in selected cases, the use of awake craniotomy, is proposed to map the cortical and subcortical eloquent areas and reduce the incidence of postoperative deficits. 11 Sociodemographic and neurosurgical data were prospectively collected, recorded, and retrospectively revised by a dedicated neurosurgeon through the Neurosurgical Complications Protocol and Database Besta-NSC. 17 The Karnofsky Performance Scale (KPS) was used to evaluate health status before surgery
Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery
Jason P. Sheehan, Chun-Po Yen, James Nguyen, Jessica A. Rainey, Kasandra Dassoulas, and David J. Schlesinger
Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone.
One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37–51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases.
The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non–small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0–11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation.
The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non–small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.
Quality of life in patients with intracranial gliomas: the impact of modern image-guided surgery
Asgeir S. Jakola, Geirmund Unsgård, and Ole Solheim
Outcome following brain tumor operations is often assessed by health professionals using various gross function scales. However, surprisingly little is known about how modern glioma surgery affects quality of life (QOL) as reported by the patients themselves. In the present study the authors aimed to assess changes in QOL after glioma surgery, to explore the relationship between QOL and traditional outcome parameters, and to examine possible predictors of change in QOL.
Eighty-eight patients with glioma were recruited from among those 16 years or older who had been admitted to the authors' department for brain tumor surgery in the period between January 2007 and December 2009. A 3D ultrasonography–based navigation system was utilized in nearly all operations and functional MR imaging data on eloquent lesions were incorporated into the neuronavigation system. Preoperative scores for QOL (EuroQol 5D [EQ-5D]) and functional status (Karnofsky Performance Scale [KPS]) were obtained. The EQ-5D and KPS scores were subsequently recorded 6 weeks postoperatively, as were responses to a structured interview about new deficits and possible complications.
There was no change in the median EQ-5D indexes following surgery, 0.76 versus 0.75 (p = 0.419). The EQ-5D index value was significantly correlated with the KPS score (p < 0.001; rho = 0.769). The EQ-5D index values and KPS scores improved in 35.2% and 24.1% of cases, were equal in 20.5% and 47.2% of cases, and deteriorated in 44.3% and 28.7%, respectively. Thus, both improvement and deterioration were underestimated by the KPS score as compared with the patient-reported QOL assessment. New motor deficits (p = 0.003), new language deficits (p = 0.035), new unsteadiness and/or ataxia (p = 0.001), occipital lesions (p = 0.019), and no use of ultrasonography for resection control (p = 0.021) were independent predictors of worsening QOL in a multivariate model.
The surgical procedures per se may not significantly alter QOL in the average patient with glioma; however, new deficits have a major undesirable effect on QOL. It seems that the active use of intraoperative ultrasonography may be associated with a preservation of QOL. The EQ-5D seems like a good outcome measure with a strong correlation to traditional variables while offering a more detailed description of outcome.
Factors involved in maintaining prolonged functional independence following supratentorial glioblastoma resection
Kaisorn L. Chaichana, Aditya N. Halthore, Scott L. Parker, Alessandro Olivi, Jon D. Weingart, Henry Brem, and Alfredo Quinones-Hinojosa
The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence.
All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection.
The median follow-up duration time was 10 months (interquartile range [IQR] 5.6–17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6–16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01).
The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.
Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma
John W. Powell, Chung T. Chung, Hemangini R. Shah, Gregory W. Canute, Charles J. Hodge, Daniel A. Bassano, Lizhong Liu, Lisa Mitchell, and Seung S. Hahn
The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies.
The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed.
The median age of the patients was 57 years (range 18–85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20–100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1–27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8–30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment–related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving ≥ 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score ≥ 70 was 7.1 months compared with 1.3 months for a KPS score ≤ 60 (p = 0.013).
Gamma Knife surgery is an effective treatment option for patients with radioresistant brain metastases. In this setting, KPS score appeared to be a more important factor in predicting survival than having > 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.