Coons, Stephen W.

1500 Background: Treatment of adult LGG is controversial. Favorable patients (pts) (age <40 years [yrs] who undergo gross total resection [GTR]) are typically observed. Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B]) are usually given initial radiation therapy (RT), reserving chemotherapy (historically procarbazine, CCNU and vincristine [PCV]) for recurrence. In 1998, the RTOG, in conjunction with SWOG, NCCTG, and ECOG initiated prospective studies of adult LGG, the results of which are reported herein. Methods: Favorable pts were observed postoperatively in a single arm Phase II study (Arm 1). Unfavorable pts were stratified by age, histology, KPS, and presence/absence of contrast enhancement on preoperative magnetic resonance imaging and randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3). Reported results include overall survival (OS) rate, median overall survival time (MOST), progression-free survival (PFS) rate, and median progression-free survival time (MPFST). Survival data are compared using Wilcoxon p-values. Results: A total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%. For the 251 unfavorable pts on Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72). MOST was not reached in RT alone pts and was 6.0 yrs in RT+PCV pts. PFS at 2- and 5-yrs was 73% and 39% with RT alone vs 72% and 61% with RT+PCV (p=0.38). MPFST was 4.0 yrs with RT alone vs 6.0 yrs with RT+PCV. Acute grade 3–4 toxicity occurred in 9% of pts who received RT alone, 67% who received RT+PCV (mostly hematologic). There were no treatment deaths on either arm. Conclusions: 5-yr PFS was poor in all three arms ranging from 39% to 61%. Only half of favorable pts were disease-free at 5 yrs. In unfavorable pts, there was no OS advantage with the addition of PCV to RT. Both PFS and MPFST were better with the addition of PCV, but not significantly. Analysis of outcome by 1p19q status is pending. No significant financial relationships to disclose.

We describe the case of a 59-year-old woman who presented with progressive bilateral vestibidar hypofunction and who was found to have bilateral granulomatous mass lesions of the mesial temporal lobe. Initially, her condition stabilized neurologically with corticosteroids, but a diagnosis of neurosarcoidosis was delayed because of the unusual presentation and persistently normal chest imaging results and serum angiotensin-converting enzyme (ACE) levels. Approximately 1 year after her initial presentation, the patient died of complications of a myocardial infarction and pulmonary embolism. Sarcoidosis should be considered in the differential diagnosis of idiopathic bilateral vestibular hypofunction even if the chest imaging and serum ACE levels are normal, particularly when there is evidence of a multisystem process.

Purpose A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). Patients and Methods Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. Results In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02). Conclusion PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.

Abstract Purpose: This study uses spatially accurate image-guided tissue analysis to evaluate the correlation between Perfusion MRI (pMRI) and tissue microvascular density parameters as markers for tumor recurrence and treatment response in high-grade glioma (HGG). Methods: Following Institutional Review Board approval, we recruited previously treated (including chemo-radiation therapy) HGG patients undergoing surgical re-resection of new enhancing lesions on surveillance MRI. Preoperatively, we acquired pMRI and contrast-enhanced stereotactic T1-Weighted (T1W) MRI data sets. Intraoperatively, we recorded stereotactic locations of multiple biopsies based on T1W data sets that guided surgery. Following surgery, we coregistered pMRI and T1W data sets to calculate localized relative cerebral blood volume (rCBV) for each stereotactic specimen location. For each specimen, we performed 1) standard H&E staining to diagnose tumor recurrence or post-treatment radiation effect (PTRE); and 2) immunohistochemical analysis with CD34 to highlight tissue vessels. We analyzed CD-34 stained slides with Axiovision Automeasure 3.4 (Zeiss, Germany) to calculate both total microvessel number (MVN) and total microvessel area (MVA), each normalized to total slide specimen area (μm2). We calculated Pearson correlations to establish relationships between a) rCBV and MVN; and b) rCBV and MVA. We also performed t-test to compare MVN, MVA, and rCBV values between tumor and PTRE samples. A neuroradiologist performed all coregistration and pMRI calculations, and a neuropathologist analyzed all tissue specimens, without knowledge of corresponding data. A biostatistician performed all statistical comparisons. Results: In this preliminary study, we included 16 tissue specimens (from 8 subjects), each diagnosed as either tumor (n=7) or PTRE (n=9). We successfully calculated localized rCBV and determined both MVA and MVN for each specimen. The rCBV values showed highest correlation with total vessel area (MVA) (r=0.65, p=0.007) and slightly less correlation with vessel number (MVN) (r=0.52, p=0.04). Tumor showed significantly higher values than PTRE for all parameters: rCBV (1.87 + 0.82 versus 0.78 + 0.2, p=.002); MVA (0.22 + 0.03 versus 0.04 + 0.007, p=0.0001); and MVN (0.0068 + 0.001 versus. 0.0016 + 0.0006, p=0.0004). Conclusion: These preliminary results show the promise of Perfusion MRI to non-invasively estimate tissue microvessel density and distinguish tumor recurrence from treatment effects. The current study is ongoing to confirm results in a larger patient population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3748.

Object In 1998, the Radiation Therapy Oncology Group initiated a Phase II study of observation for adults < 40 years old with cerebral low-grade glioma who underwent a neurosurgeon-determined gross-total resection (GTR). Methods Patient eligibility criteria included the presence of a World Health Organization Grade II astrocytoma, oligodendroglioma, or mixed oligoastrocytoma confirmed histologically; age 18–39 years; Karnofsky Performance Scale score ≥ 60; Neurologic Function Scale score ≤ 3; supratentorial tumor location; neurosurgeon-determined GTR; and pre- and postoperative MR imaging with contrast enhancement available for central review by the principal investigator. Patients were observed following GTR and underwent MR imaging every 6 months. Prognostic factors analyzed for their contribution to patient overall survival, progression-free survival (PFS), and tumor recurrence included age, sex, Karnofsky Performance Scale score, Neurologic Function Scale score, histological type, contrast enhancement on preoperative MR imaging, preoperative tumor diameter, residual disease based on postoperative MR imaging, and baseline Mini-Mental State Examination score. Results Between 1998 and 2002, 111 eligible patients were entered into the study. In these 111 patients, the overall survival rates at 2 and 5 years were 99 and 93%, respectively. The PFS rates in these 111 patients at 2 and 5 years were 82 and 48%, respectively. Three prognostic factors predicted significantly poorer PFS in univariate and multivariate analyses: 1) preoperative tumor diameter ≥ 4 cm; 2) astrocytoma/oligoastrocytoma histological type; and 3) residual tumor ≥ 1 cm according to MR imaging. Review of the postoperative MR imaging results revealed that 59% of patients had < 1 cm residual disease (with a subsequent 26% recurrence rate), 32% had 1–2 cm residual disease (with a subsequent 68% recurrence rate), and 9% had > 2 cm residual disease (with a subsequent 89% recurrence rate). Conclusions These data suggest that young adult patients with low-grade glioma who undergo a neurosurgeondetermined GTR have a > 50% risk of tumor progression 5-years postoperatively, warranting close follow-up and consideration for adjuvant treatment.