preoperative prognostic classiﬁcation system for …...j. neurosurg. / volume 109 / november 2008...

J. Neurosurg. / Volume 109 / November 2008

J Neurosurg 109:000–000, 2008

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P UBLISHED survival estimates for patients with LGGs range from 3 to > 20 years.2,7,8,12,14,16,17,20,23 The typi-cally slow growth of these neoplasms requires ex-

tensive follow-up, which has limited the number of stud-ies in the MR imaging era that have adequately addressed long-term outcomes. Consequently, there are few current

evidence-based standards for guiding the medical and surgical treatment of patients with LGGs.

Although some studies have addressed patient clini-cal status and tumor imaging features, they have not taken into consideration other factors that can affect the resect-ability of LGGs. Tumor invasion of functionally eloquent areas of the brain and diffuse lesion borders, for example, are critical factors that affect whether radical removal or GTR is feasible.

The lack of studies addressing these issues has led to controversy regarding the appropriate management of LGGs. Some clinicians have advocated simple observa-tion, whereas others have recommended maximal resec-


J Neurosurg 109:817–824, 2008

Preoperative prognostic classification system for hemispheric low-grade gliomas in adults

Clinical article

EDWARD F. CHANG, M.D., JUSTIN S. SMITH, M.D., PH.D., SUSAN M. CHANG, M.D., KATHLEEN R. LAMBORN, PH.D., MICHAEL D. PRADOS, M.D., NICHOLAS BUTOWSKI, M.D., NICHOLAS M. BARBARO, M.D., ANDREW T. PARSA, M.D., PH.D., MITCHEL S. BERGER, M.D., AND MICHAEL M. MCDERMOTT, M.D.Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California

Object. Hemispheric low-grade gliomas (LGGs) have an unpredictable progression and overall survival (OS) profile. As a result, the objective in the present study was to design a preoperative scoring system to prognosticate long-term outcomes in patients with LGGs.

Methods. The authors conducted a retrospective review with long-term follow-up of 281 adults harboring hemi-spheric LGGs (World Health Organization Grade II lesions). Clinical and radiographic data were collected and ana-lyzed to identify preoperative predictors of OS, progression-free survival (PFS), and extent of resection (EOR). These variables were used to devise a prognostic scoring system.

Results. The 5-year estimated survival probability was 0.86. Multivariate Cox proportional hazards modeling dem-onstrated that 4 factors were associated with lower OS: presumed eloquent location (hazard ratio [HR] 4.12, 95% confi-dence interval [CI] 1.71–10.42), Karnofsky Performance Scale score ≤ 80 (HR 3.53, 95% CI 1.56–8.00), patient age > 50 years (HR 1.96, 95% CI 1.47–3.77), and tumor diameter > 4 cm (HR 3.43, 95% CI 1.43–8.06). A scoring system cal-culated from the sum of these factors (range 0–4) demonstrated risk stratification across study groups, with the following 5-year cumulative survival estimates: Scores 0–1, OS = 0.97, PFS = 0.76; Score 2, OS = 0.81, PFS = 0.49; and Scores 3–4, OS = 0.56, PFS = 0.18 (p < 0.001 for both OS and PFS, log-rank test). This proposed scoring system demonstrated a high degree of interscorer reliability (kappa = 0.86). Four illustrative cases are described.

Conclusions. The authors propose a simple and reliable scoring system that can be used to preoperatively prog-nosticate the degree of lesion resectability, PFS, and OS in patients with LGGs. The application of a standardized scoring system for LGGs should improve clinical decision-making and allow physicians to reliably predict patient outcome at the time of the original imaging-based diagnosis. (DOI: 10.3171/JNS/2008/109/11/0817)

KEY WORDS • extent of resection • low-grade glioma • prognosis • progression • scoring • survival

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Abbreviations used in this paper: CI = confidence interval; EORTC = European Organization for Research and Treatment of Cancer; GTR = gross-total resection; HR = hazard ratio; KPS = Karnofsky Performance Scale; LGG = low-grade glioma; OR = odds ratio; OS = overall survival; PFS = progression-free survival; STR = subtotal resection; UCSF = University of California, San Francisco.

E. F. Chang et al.

818 J. Neurosurg. / Volume 109 / November 2008

tion.3,9 The precise roles of surgery and radiation therapy, although both are commonly practiced, are unclear and un likely to be resolved unless pretreatment-related fac-tors are clearly identified.

To address these questions, we analyzed an institu-tional series of patients with LGGs to identify prognosti-cators of survival and tumor progression to create a prac-tical and simple preoperative clinicoradiographic grading system for LGGs. The primary aim of this study was to devise a system for clinicians to guide therapy at the time of presentation of a patient with a nonenhancing, infiltra-tive, low-grade glial neoplasm.

Methods

We conducted a retrospective review with long-term follow-up of 281 adult patients harboring hemispheric in-filtrative LGGs surgically treated at the UCSF between January 1989 and June 2005. Patients were excluded if they had undergone any prior resection of the tumor, ex-cept a previous biopsy procedure performed as part of a diagnostic workup that led to eventual surgical removal. All included patients had histologically confirmed Grade II low-grade infiltrative gliomas (World Health Organiza-tion Grade II).10 Patients with pilocytic or gemistocytic astrocytomas were excluded. Given that the study was fo-cused on preoperative prognostication, only patients with non–contrast enhancing lesions were included for analy-sis. All research activities were approved by the UCSF in stitutional review board for human research.

All preoperative clinical and radiographic features were derived from hospital charts. Clinical variables were recorded, including patient age, sex, presence of seizures and other symptoms on presentation, and KPS score.

Preoperative MR images were reviewed while the re viewers remained blinded to patient outcome. Digital caliper measurements of the maximum tumor diameter (in any dimension) were performed using FLAIR or T2- weighted sequences. Whether tumors had discrete, well-delineated borders as opposed to diffuse, infiltrative bor-ders was also qualitatively assessed. Diffuse tumors had a more grossly infiltrative appearance, with irregular finger-like borders, in some cases crossing sulci. The well-delin-eated tumors had more regular borders that respected local anatomical boundaries. Tumor location and anatomy were carefully documented, including whether the lesion had infiltrated presumed eloquent brain areas (Fig. 1). The pre-sumed eloquent areas consisted of the sensorimotor strip (precentral and postcentral gyri), dominant hemisphere peri sylvian language areas (superior temporal, inferior frontal, and inferior parietal areas), basal ganglia/internal capsule, thalamus, and calcarine visual cortex. It is worth emphasizing the fact that this designation of presumed elo-quence is based on preoperative diagnostic anatomical MR imaging, not functional imaging or intraoperative func-tional mapping.

Surgical ProceduresDuring the study period, 8 neurosurgeons used a va-

riety of surgical methods for these lesions, ranging from a simple biopsy procedure for diagnosis alone to maximal

tolerated resection sparing functional brain areas. Some cases involved both pre- and intraoperative functional mapping when tumors were located in or directly adjacent to eloquent brain areas. Intraoperative mapping techniques included awake language and/or motor mapping. Almost all cases involved intraoperative frameless navigation.

Outcome Measures and Follow-UpThe main outcome measures were OS and PFS. Pro-

gression was defined as an unequivocal increase in the FLAIR or T2-weighted signal abnormality and/or newly detected areas of contrast enhancement on follow-up MR imaging compared with the baseline postoperative MR image obtained within 3 days after surgery. A secondary outcome measure, the extent of resection, was determined externally by neurooncologists, who used a qualitative nonvolumetric comparison of pre- and postoperative MR images. Gross-total resection was confirmed when all preoperatively demonstrated FLAIR or T2 abnormalities were absent on postoperative images. Subtotal resection was therefore any resection that was not gross total.

FIG. 1. Illustration showing presumed eloquent areas for UCSF LGG score.


Prognostic scoring system for low-grade glioma

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Follow-up information was obtained primarily through chart review, telephone interview, and the National Death Index archives. Telephone follow-up was stopped on Feb-ruary 15, 2007. The follow-up period for OS analysis was defined as the interval between the date of surgery and the date of death or the date the patient was last known to be alive. The follow-up duration for progression analysis was defined as the interval between the date of surgery and the date of the MR image on which the first progression event was detected or the date of the last known MR image with-out evidence of disease progression (whichever was first).

Devising a Scoring SystemA primary objective in this study was to devise a sim-

ple and reliable scoring system for LGGs. The predictors of the main outcome measures—OS and PFS—were used to determine which factors to incorporate in the scoring system. Continuous variables were dichotomized to facil-itate scoring. To evaluate interobserver variability among the different raters, a random subset of 200 patients was selected for blinded scoring (M.M.M. and E.F.C.) based on patient clinical history and MR images.

Statistical AnalysisStatistical analysis of potential prognostic factors for

the main outcome measures, time-to-death, and time-to-progression was performed using Cox proportional haz-ards modeling. A logistic regression was used to evaluate potential predictors of GTR. Factors that resulted in a probability value < 0.05 on univariate analysis were en-tered into multivariate analysis in a backward stepwise fashion. In cases in which multiple cutpoints for a single variable met the criterion, the case with the greatest OR or HR was selected for inclusion in the multivariate anal-ysis. Kaplan–Meier estimates were generated to illustrate the time-to-event curves. A Cohen kappa analysis was used to determine interobserver reliability.

Results

Study PopulationBaseline patient demographics and tumor character-

istics are described in Table 1. The median age was 38.2 years (range 18–72 years). Eighty-seven percent of patients presented with seizures. Forty-three patients (15.3%) had a KPS score of 100, with no tumor-related symptoms and le-sions that had been discovered as an incidental finding dur-ing evaluation for minor head trauma or another disease such as a pituitary mass. The majority of patients (79.7%) had a preoperative KPS score of 90, with minor symp-toms such as a presenting seizure or persistent headaches. Fourteen patients (5%) had a KPS score ≤ 80. Tumors were well distributed throughout the supratentorial space, pre-dominantly involving the frontal lobe (72%), temporal lobe (34%), parietal lobe (16%), insula (27%), and occipital lobe (2.5%). An eloquent location was observed in 174 cases (61.9%). Diffuse tumor borders were observed in 35% of patients. The median maximum tumor diameter was 4.6 cm (range 1.4–11 cm). The pathological subtypes of World Health Organization Grade II tumors were as follows: as-

trocytomas, 129 patients (46%); oligodendrogliomas, 112 patients (40%); and oligoastrocytomas, 49 patients (17%). Radiation was administered to 113 patients, and chemo-therapy was given to 105.

Predictors of OSSixty-six deaths occurred. The median follow-up for

those still alive was 5.8 years. The Kaplan–Meier median estimated duration of survival for the entire population was 12.0 years (range 0.2–16 years), with a 5-year sur-vival probability of 0.86. Univariate predictors of a lower rate of survival included older age, lower KPS score, elo-quent tumor location, greater lesion diameter, and diffuse tumor borders. Temporal and parietal lobe involvement, in contrast, appeared to be favorable predictors on uni-variate analysis (Table 2). The KPS score was analyzed dichotomously as ≤ 90 or ≤ 80.

Multivariate Cox proportional hazards modeling re-vealed that 4 factors were associated with a shorter OS: presumed eloquent lesion location (HR 4.12, 95% CI 1.71–10.42), KPS score ≤ 80 (HR 3.53, 95% CI 1.56–8.00), age > 50 years (HR 1.96, 95% CI 1.47–3.77), and lesion diameter > 4 cm (HR 3.43, 95% CI 1.43–8.06; Table 3 and Fig. 1).

The maximum lesion diameter was dichotomized at 4 cm in the multivariate analysis because it was the size

TABLE 1Summary of characteristics in 281 adults harboring LGGs

Characteristic No. (%)

age in yrs60 8 (2.8)

51–60 28 (10.0)41–50 82 (29.2)31–40 108 (38.4)18–30 55 (19.6)

age at op in yrs median 38.2range 18–72

female sex 110 (39.1)KPS score

100 43 (15.3)90 224 (79.7)80 13 (4.63)70 1 (0.35)

history of seizures 245 (87.2)lesion location

frontal 201 (72)temporal 96 (34)parietal 44 (15.6)insula 77 (27.4)occipital 7 (2.5)

lt side involved 148 (52.6)eloquent brain involved 174 (61.9)diffuse tumor borders 99 (35.2)max tumor diameter in cm

median 4.6range 1.4–11

tumor diameter in cm6.0 74 (26.4)

5.1–6.0 46 (16.4)4.1–5.0 67 (23.9)3.1–4.0 40 (14.3)2.1–3.0 41 (14.6)

2 13 (4.6)

E. F. Chang et al.


cut off associated with the greatest HR (7.09) on univari-ate analysis. If the maximum diameter was used instead of the dichotomous variable, it did not appear to be signif-i cant when entered as a continuous variable in the back-ward stepwise regression. Notably, only 17 deaths occurred among the 148 patients with tumors based in noneloquent areas of the brain.

Predictors of PFSOne hundred thirty-four progression events were ob-

served. The median follow-up was 4.9 years in patients who did not have tumor progression. The Kaplan–Meier estimated median time to radiographically demonstrated progression was 3.57 years (range 0.3–13 years). Univari-ate analysis showed that eloquent brain involvement, pa-

tient age (> 30 years only), KPS score, and greater maxi-mum lesion diameter were associated with a worse rate of PFS (p < 0.05, HR > 1). In contrast, parietal lobe involve-ment was associated with improved PFS (Table 2).

Multivariate Cox proportional hazards modeling dem-onstrated that a presumed eloquent tumor location was the only predictor associated with lowered PFS (HR 2.53, 95% CI 1.71–3.75; Table 3).

Predictors of STR and GTRGross-total resection was achieved in 92 patients

(33%), and STR in 189 patients (67%). Univariate logistic regression analysis showed that a history of seizures, an eloquent lesion location, tumor diameter, diffuse tumor borders, and temporal and insular lobe involvement were associated with STR. Parietal lobe involvement was as-sociated with a greater likelihood of GTR (Table 2).

Multivariate logistic regression showed that 4 factors increased the odds of STR: presumed eloquent tumor loca-tion (OR 9.20, 95% CI 4.57–18.52), diffuse lesion borders (OR 3.12, 95% CI 1.29–7.78), temporal lobe in volvement (OR 2.35, 95% CI 1.02–5.44), insular lobe in volvement (OR 6.93, 95% CI 1.89–25.4), and greater maximum tumor diameter (OR 1.36, 95% CI 1.12–1.68). In contrast, parietal lobe tumors appeared to have a relatively increased likeli-hood of GTR (OR 0.32, 95% CI 0.13–0.77; Table 3).

Evaluation of a Proposed Preoperative Scoring SystemA scoring system was created based on our determi-

nation of the prognostic factors for OS. In the scoring sys-tem, 1 point was assigned for each factor present. The fi-nal score is the total number of points assigned. The final 4 factors chosen were as follows: 1) presumed eloquence

TABLE 2Univariate predictors of OS, PFS, and extent of resection

OS PFS STR

Factor p Value HR (95% CI) p Value HR (95% CI) p Value OR (95% CI)

age (yrs) 0.012 1.03 (1.01–1.06) 0.26 0.99 (0.97–1.01) 0.503 1.01 (0.98–1.04)30 0.2275 1.51 (0.33–2.98) 0.05 1.48 (1.01–2.21) 0.5206 0.81 (0.42–1.54)40 0.1518 1.43 (0.43–2.35) 0.22 1.27 (0.89–1.80) 0.2334 1.36 (0.82–2.77)50 0.001 3.52 (0.16–6.32) 0.99 0.99 (0.52–1.91) 0.3061 1.52 (0.68–3.38)60 0.0393 3.42 (0.09–11.1) 0.83 0.89 (0.28–2.79) 0.638 1.47 (0.29–7.46)

KPS score 0.001 0.85 (0.80–0.90) 0.0027 0.93 (0.88–0.97) 0.001 0.88 (0.83–0.94)90 0.0569 3.09 (0.97–9.67) 0.7341 1.58 (0.52–2.05) 0.002 3.60 (1.85–7.07)80 0.0001 8.33 (3.92–17.5) 0.0196 3.57 (1.83–6.06) 0.9733 0.58 (0.25–1.34)

seizures 0.1079 1.48 (0.78–3.2) 0.75 0.97 (0.68–1.40) 0.0113 2.47 (1.23–4.98)female sex 0.9827 0.994 (0.60–1.65) 0.85 0.97 (0.68–1.37) 0.48 1.19 (0.72–1.97)eloquent brain involved 0.0001 7.81 (3.05–18.18) 0.0001 2.53 (1.71–3.76) 0.0001 11.92 (6.60–21.53)max tumor diameter in cm 0.0027 1.21 (1.07–1.37) 0.0002 1.18 (1.08–1.29) 0.0001 1.74 (1.46–2.08)

6 0.1261 1.55 (0.88–2.74) 0.0003 1.98 (1.37–2.86) 0.0001 6.67 (2.92–15.24)5 0.0006 2.42 (1.45–4.03) 0.0021 1.72 (1.22–2.44) 0.0001 5.28 (2.90–9.62)4 0.0001 7.09 (3.16–15.87) 0.0012 1.90 (1.29–2.81) 0.0001 4.91 (2.86–8.41)3 0.0039 3.04 (1.42–6.49) 0.0067 1.92 (1.20–3.07) 0.0001 4.05 (2.18–7.51)2 0.5185 1.59 (0.39–6.53) 0.0915 1.37 (0.76–5.59) 0.03 3.51 (1.11–11.03)

diffuse tumor borders 0.0001 3.18 (1.98–8.00) 0.0611 1.39 (0.98–1.95) 0.0001 4.53 (2.59–7.93)tumor location

frontal 0.856 1.05 (0.61–1.82) 0.9797 0.98 (0.67–1.44) 0.88 0.96 (0.56–1.65)temporal 0.029 0.58 (0.35–0.97) 0.18 0.78 (0.55–1.12) 0.0001 4.98 (2.63–9.41)parietal 0.0012 0.42 (0.24–0.71) 0.0145 0.58 (0.38–0.89) 0.023 0.49 (0.24–0.90)insula 0.955 0.65 (0.38–1.09) 0.14 0.76 (0.53–1.10) 0.0001 19.09 (5.82–62.59)occipital 0.984 1.01 (0.25–4.16) 0.62 0.80 (0.33–1.95) 0.71 1.37 (0.26–7.16)

TABLE 3Multivariate predictors of OS, tumorprogression, and extent of resection

Factor p Value HR (95% CI)

OSeloquent brain involved 0.0018 4.12 (1.71–10.42)KPS score 80 0.0025 3.53 (1.56–8.00)patient age 50 yrs 0.0412 1.96 (1.47–3.77)tumor diameter 4 cm 0.0014 3.43 (1.43–8.06)

tumor progressioneloquent brain involved 0.0001 2.53 (1.71–3.75)

STReloquent brain involved 0.0001 9.20 (4.57–18.52)diffuse borders 0.01 3.12 (1.29–7.78)temporal lobe location 0.0447 2.35 (1.02–5.44)max tumor diameter 0.0034 1.36 (1.12–1.68)insular location 0.0035 6.93 (1.89–25.46)parietal lobe location 0.017 0.32 (0.13–0.77)



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involved (Y/N), 2) KPS score ≤ 80 (Y/N), 3) patient age > 50 years (Y/N), and 4) tumor diameter > 4 cm (Y/N; Table 4).

The scoring system was then applied to our data set. Highly significant differences were observed for OS and progression by using the UCSF LGG scoring system (p < 0.001, log-rank test), effectively stratifying the study population into low (Scores 0–1), intermediate (Score 2), and high risk (Scores 3–4) groups. Scores of 0 and 1 were combined, as were Scores of 3 and 4, because there were few patients in each category and only minimal differ-ences between the groups (between 0/1 and 2: p < 0.0001, log-rank test; between 2 and 3/4: p < 0.001, log-rank test). The 5-year cumulative OS probabilities were as follows: Scores 0–1 = 0.97, Score 2 = 0.81, and Scores 3–4 = 0.56. The 5-year PFS probability estimates were as follows: Scores 0–1 = 0.76, Score 2 = 0.49, and Scores 3–4 = 0.18 (Fig. 2 and Table 5). Four examples of the scoring system application are shown in Fig. 3.

To determine the interobserver reliability of the grading system, 200 randomly selected patient profiles and MR images were blindly scored by a neurosurgeon attending (M.M.M.) and resident (E.F.C.). A high con-cordance was found with an overall kappa value of 0.86 (Table 6). The eloquent location variable accounted for the majority of the variance (kappa = 0.82).

Discussion

We devised a preoperative scoring system for long-term prognostication in patients with hemispheric LGGs. Four variables (areas of eloquence, patient age > 50 years, KPS score ≤ 80, and lesion diameter > 4 cm) were predic-tive of survival on multivariate analysis and were there-fore used for the scoring system.

The main advantages of the proposed scoring system are its simplicity and reliability. The results highlight the predictive value of preoperative clinical and radiographic factors, some of which affect the resectability of LGGs. The application of this scoring system will, we hope, aid clinicians in providing prognostic information to patients at presentation during surgical planning and will allow standardization of surgical and adjuvant therapy clinical trials.

Several of the predictors in this study have been identified in other series. Patient age, for example, has been the most well-established predictor of survival in several multivariate analyses.2,12–14,17,20,21 Whereas others have shown a linear relationship between patient age and survival, we observed that patients > 50 years old had a specifically increased risk of death. The cause of this

association is unclear but may involve a more malignant underlying biology related to an advanced age1 as well as natural life expectancy, higher incidence of other diseas-es, and general vulnerability to illness. Studies that have documented the cause of death in patients with LGGs are likely to better address this issue.

A poor KPS score is another well-documented predic-tor of survival in other studies.4,11,13–15 Although KPS is a fairly nonspecific indicator of functional status, our analy-sis confirms its relevance to long-term prognostication. The majority of patients had a KPS score of 90 or 100 at the time of surgery, but a minority of patients with a KPS score of ≤ 80 had a distinctly worse rate of survival. In our patient population, medically refractory uncontrolled seizures and neurological deficits accounted for almost all the cases in which the KPS score was < 90. Fortunately, an advanced age and poor functional status are risks factors that apply to the minority of patients with LGGs.

Whereas age and KPS score are important clini-cal predictors, we found that radiographically identified

FIG. 2. Graphs showing long-term OS (upper) and PFS (lower) in patients after resection of LGG. Cum. = Cumulative.

E. F. Chang et al.


features of LGGs were also critical and in fact are more central in predicting PFS. Tumor size and eloquent brain involvement were both strong predictors of STR, and thus it is not surprising that these factors also affected PFS and long-term OS.

Tumor size has been identified as an important predic-tor in several studies.2,3,8,11 Tumor size appeared to linearly predict survival in the present series of patients, but a cut-off at 4 cm was designated mainly to separate bigger from smaller tumors in general. Gross-total resection is more difficult to achieve with larger infiltrative tumors,3 and these lesions reflect a more extensive disease burden.

To our knowledge, this is the first study which has dem onstrated the long-term significance of an eloquent tu-mor location on patient survival. Because LGGs typically grow slowly and often spare neural function as they infil-trate eloquent brain areas, resection in many cases can be dangerous and limited, especially when performed with-out functional mapping. Recent studies involving magnetic source imaging have confirmed functional activity within LGGs.5,18,19 In our series, more than half of the patients had tumors that involved areas located in, or directly adjacent to, presumed eloquent regions. Among the 148 patients with tumors located outside pre sumed eloquent areas, we observed only 17 deaths, which highlights the strong pre-dictive value of presumed eloquence. Low-grade gliomas located in eloquent brain regions can cause more neurolog-ical impairment and preclude complete debulking of the tu mor burden.

Other imaging features of these tumors were evalu-ated in devising our scoring system. The presence of dis-crete tumor borders on the T2-weighted MR images was not a prognostic factor for either time to progression or survival. It was the senior author’s (M.M.M.) impression that a discrete border would make complete resection more likely regardless of an eloquent or noneloquent lo-cation. This proved not to be the case.

The prospective multicenter Phase III EORTC trials 22844 and 22845, which were focused on the role of ra-diation therapy dose effects and timing, respectively, also generated similar predictors.8,17,23 Although differences in

radiation dose and timing did not appear to affect survi-val, several pretreatment clinical and imaging factors were identified as important for long-term survival (older age, presence of preoperative neurological deficits, larg-est tumor diameter, and tumor crossing the midline).

Our study confirmed some of these predictors, but there were some notable differences in methodology and findings. The median survival in the EORTC trial was ~ 7.3 years, whereas the median survival in our series was considerably longer at 12.0 years. The reason for this discrepancy is unclear but may reflect advances in early diagnosis and surgical management; the EORTC trials were initiated almost a decade before the present study. Furthermore, CT as opposed to MR imaging was the pri-mary modality used in the EORTC trials. Only 3 patients in our series had LGGs crossing the midline and were therefore not analyzed (too few patients for analysis). More importantly, the effect of an eloquent tumor loca-tion on patient survival was absent from the EORTC trial and other previous studies. In the present retrospective study, however, issues of treatment selection bias could not be accounted for.

Although our scoring system is simple and easy to apply, it is only meant to guide prognosis and clinical management and research in the preoperative setting. Several advantages in this study included the following: 1) all patients underwent imaging studies after the wide-spread adoption of MR imaging; 2) a uniform histological diagnosis was conducted by an independent centralized pathology review; 3) telephone interviews and MR imag-ing reviews were conducted to ensure the best follow-up data possible. Nonetheless, other known prognosticators such as the 1p-19q deletion from tissue specimens6,22 and the actual extent of resection based on postoperative im-aging are likely to improve the prediction of long-term survival. More accurate modeling could be accomplished by using actual patient ages and tumor sizes for prognos-tication as opposed to simple cutoffs. This scoring system should be validated at other institutions. We will attempt to validate the findings of this study by having other insti-tutions apply the scoring system to patients with LGGs.



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Conclusions

In this study, we derived a simple and reliable pre-operative scoring system for the long-term OS of patients with LGGs. The LGG score is the sum of the presence of 4 factors: involvement of a presumed eloquent location, KPS score ≤ 80, patient age > 50 years, and maximal lesion di-

ameter > 4 cm. The total score was inversely proportional to predicted survival. We also evaluated prognosticators for PFS and extent of resection. The application of a stan-dardized scoring system for LGGs should improve clinical decision-making and help guide future research efforts.

Acknowledgment

We thank Kenny Chung for his help in preparing the manu-script.

Disclaimer

The authors report no conflict of interest concerning the mate-rials or methods used in this study or the findings specified in this paper.

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FIG. 3. Four example applications of the UCSF LGG scoring system. A: Score 1: A T2-weighted MR image obtained in a 35-year-old man who had presented with a generalized tonic-clonic seizure, revealing a discrete, well-delineated, 3.2-cm right frontal hyperintense mass, with no abnormal enhancement. B: Score 2: A T2-weighted MR image obtained in a 34-year-old woman with a 3-month history of progressively worsening numb-ness in her left hand, showing a diffuse, ill-defined focus of T2 prolongation in the right frontal lobe measuring 2.2 cm in maxi-mum diameter. This lesion was considered to be in a region of eloquence because it was situated directly adjacent to and overly-ing the precentral gyrus (motor strip), at the expected location of the hand representation. C: Score 3: An MR image obtained in a 22-year-old woman with persistent headaches for > 2 years, demonstrating an 8.5-cm left temporal nonenhancing lesion with heterogeneous T2 prolongation and involving presumed eloquent perisylvian language areas. D: Score 4: An MR image obtained in a 59-year-old man who had presented with a history of com-plex partial seizures during the past 4 years, revealing T2 prolon-gation in the left insular region involving the medial and anterior temporal lobe, inferior frontal cortex, and basal ganglia regions and measuring 5.2 cm in maximum diameter.

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Manuscript submitted October 1, 2007.Accepted January 23, 2008.Address correspondence to: Edward F. Chang, M.D., Department

of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, M779, San Francisco, California 94143. email: [email protected].

preoperative prognostic classiﬁcation system for …...j. neurosurg. / volume 109 / november 2008...

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