Risk Of Leptomeningeal Disease Research Articles

Post-Operative Stereotactic Radiotherapy for Resected Brain Metastases: Results of the Multicenter Analysis (AURORA) of the German Working Group "Stereotactic Radiotherapy"

While the results of prospective studies support the use of postoperative stereotactic radiotherapy (RT) to the resection cavity (RC) as the standard of care after surgery, there are several issues that need to be investigated such as factors for improving local control, risk of leptomeningeal disease and radiation necrosis. Further, the optimal dose and fractionation is still under debate. The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology (DEGRO) analyzed its multi-institutional database with 661 patients who received postoperative stereotactic RT to the RC. Treatment was performed at 13 centers between 2008 and 2021. Patient characteristics, treatment details, and follow-up data including overall survival (OS), local control (LC) were evaluated. Cox Regression and Kaplan-Meier curves with Log-rank Tests were calculated for selected variables. In this retrospective study, overall survival was 61.5% at 1 year, 47.6% at 2 years, and 35.5% at 3 years, and local control was 84.6% at 1 year, 74.8% at 2 years, and 72.8% at 3 years. 96% of patients were treated with hypofractionated stereotactic radiotherapy (HSRT), only 26 patients received single fraction radiosurgery (4%). Prognostic factors associated with overall survival were Karnofsky Performance Status, RPA and GPA class, controlled primary tumor and absence of extracranial metastases, whereas prognostic factor associated with local control was planning target volume (23 mL or less). HSRT is the most common fractionation form in the treatment of RCs in this multicenter analysis. This approach results in excellent OS and LC outcomes. OS in patients with resected brain metastases is mainly influenced by performance status. In regard to local control, RT of large cavities remain a challenge with significantly worse outcome.

Stereotactic radiosurgery versus whole-brain radiotherapy after resection of solitary brain metastasis: A systematic review and meta-analysis

ObjectiveThe standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline. MethodsWe performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients’ neurocognitive function and quality of life after each postoperative radiation form. ResultsFour studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51–1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49–2.98, p = 0.67, I2 = 18%), neither in the patients’ overall survival (HR = 1.06, CI = 0.61–1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94–4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group. ConclusionsAlthough SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

Utilization of neoadjuvant stereotactic radiosurgery for the treatment of brain metastases requiring surgical resection: a topic review.

Following surgical resection of brain metastases (BMs), adjuvant stereotactic radiosurgery (SRS) has become the standard of care post-operative cavity irradiation. Recent studies, however, have demonstrated that with the current sequence of surgery and radiation, risk of leptomeningeal disease (LMD) and radiation necrosis (RN) remains high. Pre-operative, or neoadjuvant, SRS (nSRS) has been proposed as an alternative treatment strategy which not only minimizes local recurrence (LR) but also LMD and RN. It is thought that nSRS sterilizes the tumor, allowing for minimal spillage of viable tumor cells during resection, creating less favorable conditions for LMD. Furthermore, nSRS allows for easier contouring and decreased margin irradiation during planning and treatment, respectively, diminishing the risk of symptomatic RN. While nSRS has already been adopted for treating other extra-cranial tumors, its role in treating BMs is yet to be defined. We aim to summarize recent studies in nSRS usage for BMs and the rationale of this treatment strategy. We performed a search for articles regarding nSRS for BMs published in PubMed from 2018 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized a total of 14 retrospective reviews, case series, dose/timing studies, and ongoing Phase II & III clinical trials. In this review, we describe the findings of current studies and identify prospective clinical trials with the aim of understanding the efficacy of nSRS over current treatment standards. Herein, we also discuss the theoretical advantages and limitations of nSRS (both biologic and clinical) to help guide future clinical investigations.

Preoperative stereotactic radiosurgery in the management of brain metastases and gliomas.

Stereotactic radiosurgery (SRS) is the delivery of a high dose ionizing radiation in a highly conformal manner, which allows for significant sparing of nearby healthy tissues. It is typically delivered in 1-5 sessions and has demonstrated safety and efficacy across multiple intracranial neoplasms and functional disorders. In the setting of brain metastases, postoperative and definitive SRS has demonstrated favorable rates of tumor control and improved cognitive preservation compared to conventional whole brain radiation therapy. However, the risk of local failure and treatment-related complications (e.g. radiation necrosis) markedly increases with larger postoperative treatment volumes. Additionally, the risk of leptomeningeal disease is significantly higher in patients treated with postoperative SRS. In the setting of high grade glioma, preclinical reports have suggested that preoperative SRS may enhance anti-tumor immunity as compared to postoperative radiotherapy. In addition to potentially permitting smaller target volumes, tissue analysis may permit characterization of DNA repair pathways and tumor microenvironment changes in response to SRS, which may be used to further tailor therapy and identify novel therapeutic targets. Building on the work from preoperative SRS for brain metastases and preclinical work for high grade gliomas, further exploration of this treatment paradigm in the latter is warranted. Presently, there are prospective early phase clinical trials underway investigating the role of preoperative SRS in the management of high grade gliomas. In the forthcoming sections, we review the biologic rationale for preoperative SRS, as well as pertinent preclinical and clinical data, including ongoing and planned prospective clinical trials.

LOCL-06 SUPERVISED MACHINE LEARNING IDENTIFIES RISK FACTORS ASSOCIATED WITH LEPTOMENINGEAL DISEASE AFTER SURGICAL RESECTION OF BRAIN METASTASES

BACKGROUNDResection of brain metastases (BMs) can help with local disease control, yet predictors of leptomeningeal disease (LMD) after surgery are not well defined. This study examined rates and predictors of LMD in patients who underwent resection of a BM. METHODSA retrospective, single-center study was conducted examining LMD risk for adult patients with a BM that underwent resection with postoperative adjuvant radiation. Logistic regression analyses and a supervised machine learning algorithm (Random forest) were implemented to identify factors within the cohort that were associated with LMD. RESULTSOf the 182 patients in the cohort, 43 patients (23.6%) developed LMD in the postoperative setting with 18 cases of classical LMD (9.9%) and 25 cases of nodular LMD (13.7%). Median censored time to LMD was not reached, and 6-, 12-, and 24-month LMD-free rates from surgery were 93%, 86.3%, and 71.8%, respectively. Median time from surgery to classical and nodular LMD were 13.1 and 9.5 months, respectively (Log-rank p=0.71). Patients diagnosed with classical LMD had worse survival outcomes from LMD diagnosis compared to nodular LMD (2.6 vs 9.7 mo, Log-rank p=0.02), and LMD-subtype was significantly associated with overall survival from the date of surgery (classical vs nodular vs none: 16.1 vs 20 vs 36.7 mo, p <.0001). Random forest analysis identified primary cancer type, absence of extracranial disease, and tumor volume as the top 3 factors associated with LMD. On multivariate regression analysis, absence of extracranial disease at index surgery was associated with any LMD (OR 2.65, 95% CI 1.15-6.10, p=0.02). Treatment with postoperative checkpoint inhibitors, type of radiation, and performing additional craniotomies were not associated with risk of LMD. CONCLUSIONSClassical-type LMD is associated with worse prognosis compared to nodular-type LMD. Absence of extracranial disease at the time of surgery was the most consistent factor associated with LMD on follow-up.

OMRT-9. Effect of Pre-Operative Stereotactic Radiosurgery on Brain Metastasis: Analysis of DNA and RNA Genomic Profiles from Phase-II Clinical Trial NCT03398694

BackgroundWith improved systemic therapy that has limited impact on the intracranial compartment, the incidence of brain metastasis (BM) from solid cancers is rising and negatively impacting patient’s overall survival (OS). Treatment varies based on presentation, however, for patients with <4 symptomatic BMs current clinical practice involves surgical resection followed by stereotactic radiosurgery (SRS) to the resection cavity. Post-operative SRS is associated with increased risk of leptomeningeal disease (LMD) and local recurrence in the follow-up period. We hypothesize that pre-operative SRS will decrease the incidence of LMD as well as local recurrence and increase patient’s OS by delivering a lethal dose of radiation to tumor cells before they are disturbed by surgical resection. In a Phase II clinical trial (NCT03398694) we are treating patients with 1–4 symptomatic BMs with pre-operative SRS while collecting DNA and RNA sequencing data from core and peripheral edges of the resected tumor to examine the genomic effects of SRS on tumor.MethodsPost-SRS resected tumor specimens were divided into two groups: ‘center’ and ‘periphery’ with respect to the center of SRS treatment with periphery within 50% isodose line. Previously resected untreated BMs were used as control. DNA and RNA were isolated from all samples for sequencing.ConclusionsOur initial analyses show that pre-treatment with SRS, results in significant genomic changes at DNA and RNA levels throughout the tumor, in both center as well as periphery. Furthermore, significant transcriptomic differences were noted among matched samples between the central and peripheral SRS locations implicating differential effect of SRS dosing within a tumor. Initial gene ontological analysis on non-small cell lung cancer samples demonstrated an overexpression of WNT and BMP signaling pathways (p <.001, p<.01). These pathways are typically involved in neuronal development, hinting that adaptation to the brain microenvironment was occurring post SRS treatment.

Abstract PS14-08: Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease

Abstract BACKGROUNDImprovements in systemic therapies have led to significantly improved survival in patients with breast cancer and have created a challenge with regards to management of brain metastases (BM) and leptomeningeal disease (LMD). LMD is a highly aggressive condition, resulting in rapid neurological decline and a short survival of weeks to months. The purpose of this study is to identify clinical factors that can predict for LMD when a patient is diagnosed with BM, and to assess outcomes with various treatment modalities.METHODSA retrospective analysis was conducted using a clinical database at a single institution and included 178 patients with breast cancer and treated BM between 2007-2020. Demographic, clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cytology or neuroimaging. Chi-square and t-test were used.RESULTSOut of 178 patients with breast cancer and treated BM, 41 (23%) developed LMD. Median age for the study cohort was 51.3 +-13.4 years; those with LMD was 47.9 +-12.3 (p=0.057) years. One of the 178 patients was a male and all 41 with LMD were females. There were 58.5% Caucasian women in the LMD group followed by African-American being 24.4% (p=0.31). Characteristics like number of brain lesions (p=0.57), median size of the largest brain lesion (p=0.70), hemorrhagic/cystic lesions (p=0.68), systemic disease being progressive in 42.6%, stable in 19.3% and 26.1% with no evidence of systemic disease at the time of diagnosis of BM (p=0.34) did not pose a higher risk in developing LMD. For 29% patients the brain lesions were supratentorial, 23.7% were infratentorial and 47.4% patients had both and had a higher risk for LMD (p=0.025). Patients with liver (p=0.45) and bone (p=0.48) lesions did not have higher risk for LMD which was seen in those without lung metastases (p=0.03). In the LMD group, 39% had HR+, 31.7% HER2+, and 41.4% had triple negative breast cancer (TNBC). The higher incidence of HR+ patients could be attributed to the fact that the more aggressive HER2+ and TNBC patients may have not gotten treatment for their BM as they pursued comfort care status. In the LMD group, 13.1% received prior stereotactic radiation, 39.5% whole brain radiation, 10.5% had surgery alone and 36.8% had surgery with pre/post-op radiation. Patients who had any surgery did not have a higher risk for LMD (p=0.26). Surgery did not pose a higher risk for local recurrence, seen in 28% patients (p=0.42) and occurrence of BM at another site, seen in 36.5% patients (p=0.16). CONCLUSIONSAmong breast cancer patients with brain metastases those who develop LMD tend to be younger, with higher risk in Caucasians and African-American women; however, this was not statistically significant. The number, size, hemorrhagic/cystic character of brain lesions did not pose a higher risk whereas occurrence of synchronous lesions in supratentorial and infratentorial locations increased risk of LMD. There was no statistically significant difference in the rates of LMD, local recurrence, CNS recurrence at another site with surgery and/or radiation. EthnicityBrain metastases (N=178)LMD group (N=41) (p=0.31)Caucasian58.4%58.5%Hispanic12.4%4.9%African-American19.1%24.2%Others10.1%12.2% Clinical characteristicsBrain metastasesLMD groupP valueNumber of brain lesions (Median interquartile range)3 (1-8)2.5 (1-9)P=0.57Median size of the largest brain lesion (cm)2.4 1.42.53 1.69p=0.70Hemorrhagic lesions223P=0.68Cystic lesions163 Citation Format: Akshjot Puri, Charisma Mylavarapu, Jiagiong Xu, Tejal A Patel, Bin S Teh, Ivo Tremont-Lukats, Jenny C Chang, Polly Niravath. Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-08.

Long Term Outcomes And Patterns Of Failure After Single Fraction Preoperative Radiosurgery For Brain Metastases

Postoperative (post-op) radiosurgery (SRS) after resection of brain metastases (BM) is associated with up to 30% risk of leptomeningeal disease (LMD). Approximately 60-70% of LMD is nodular pattern in this setting, which is thought to be associated with surgical tumor spillage. We have previously demonstrated that preoperative (pre-op) SRS is a feasible alternative to post-op SRS. Herein we report patterns of failure and long terms outcomes for patients (pts) treated with pre-op SRS. The records for pts with BM treated with pre-op SRS and planned surgical resection were reviewed. Pts with classically radiosensitive tumors, prior or planned adjuvant whole brain radiotherapy (WBRT), or no cranial imaging ≥ 1 month after surgery were excluded. Pre-op SRS dose was based on lesion size and was reduced approximately 10-20% from standard. No gross tumor volume (GTV) margin expansion was used. Surgery generally followed within 48 hours. Overall survival (OS) was estimated using the Kaplan-Meier method. Intracranial event rates were estimated using cumulative incidence with competing risk of death. Radiographic pattern of LMD was classified as classical “sugarcoating” (cLMD) vs. nodular (nLMD). The study cohort consisted of 141 pts with 150 lesions treated with single fraction pre-op SRS followed by planned surgery between 2005 – 2018. Most pts had a single BM (67%), underwent gross total resection (GTR, 96%), and had non-small cell lung cancer (41%). Median interval between pre-op SRS and surgery was 2 days, median SRS dose was 15 Gy, and median GTV volume was 8.4 cc (approximately equivalent to 2.5 cm diameter lesion). The 2-year cavity local recurrence (LR) rate was 23% overall and 20% in pts status post GTR. Five of 6 pts status post subtotal resection experienced LR. Multivariate analysis demonstrated GTR and renal cell histology as significantly associated with reduced risk of LR. SRS dose, lesion volume, and time between pre-op SRS and surgery were not significant. The 2-year LMD rate was 5%. Two of the 9 patients with LMD (22%) had nLMD while 78% had cLMD. The 2-year radiation necrosis (RN), symptomatic RN, and non-LMD distant brain failure rate was 7%, 4%, and 58%, respectively. Median OS was 19 months. Thirty-seven pts with 40 lesions had long term (≥2 years of cranial imaging) follow-up. In this subset, the 5-year cavity LR, symptomatic RN, and LMD rate was 25%, 8%, and 12%, respectively. Single fraction pre-op SRS is an effective treatment for surgically resected BM with low rates of cavity LR, RN, and LMD. LMD after pre-op SRS seems to be distinct from post-op SRS with a lower overall rate and lower proportion of nLMD pattern, which supports pre-op SRS sterilization of surgical tumor spillage. Outcomes in pts with long term imaging follow-up are consistent with the overall cohort. These data support further studies of pre-op SRS, including a randomized trial of pre-op vs. post-op SRS.

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease

PurposeSurgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S + SRS) versus FSRT alone. Methods and MaterialsWe identified all patients with a brain metastasis ≥3 cm in diameter treated from 2004 to 2017 with S + SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the χ2 test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups. ResultsA total of 125 patients were identified, including 82 and 43 in the S + SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S + SRS and FSRT groups was 2.5 and 1.5, respectively (P < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S + SRS and FSRT groups was 45% and 19%, respectively (P = .048). The KM estimate of 12-month local control in the S + SRS and FSRT groups was 70% and 69%, respectively (P = .753). The 12-month KM estimate of grade ≥3 toxicity was 1.4% in S + SRS group versus 6.3% in the FSRT alone group (P = .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups (P = .257). ConclusionsSurgery is appropriate for certain brain metastases, but S + SRS may increase LMD risk compared with FSRT alone. Because S + SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S + SRS in select patients with large brain metastases.

Timing, presentation, and patterns of failure of leptomeningeal disease after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.

2070Background: Postoperative (post-op) radiosurgery (SRS) has been proposed as a standard of care based on 2 phase III trials, but has been associated with up to 30% risk of leptomeningeal disease...

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease

Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

We sought to determine the risk of LMD in patients treated with stereotactic radiosurgery (SRS) targeting the post-operative cavity following surgical resection of a brain metastasis, deferring whole brain irradiation in all patients. We retrospectively reviewed 161 brain metastasis resection cavities in 153 patients treated from 1998 to 2011 with post-operative SRS. No patient had prior WBI. LMD was defined through radiologic and/or pathologic findings. The Kaplan-Meier overall survival, local cavity, distant parenchymal brain and distant LMD brain failure rates were calculated. Control rates were censored at the time of last follow-up or at the time of salvage whole brain irradiation. Statistically significant factors associated with LMD were determined through univariate analysis. Factors analyzed included: Histology (Lung, Colon, Breast, Melanoma, Gynecologic, Other), location of tumor at the pial surface (Yes vs. No), posterior fossa versus supratentorial location, en bloc versus piecemeal/indeterminate resection. Median follow-up was 12 months (range 1-114 months). Median overall survival was 18 months (range 1-114 months). Local cavity control at 1 and 2 years was 87% and 81%. Eighteen patients (11% of cavities) developed LMD at a median of 5 months (range 2-33 months) following SRS. Five of 18 were isolated LMD failures; 13 of 18 had additional new parenchymal metastases. The 1 and 2 year risk of LMD was 13%. Posterior fossa (p = 0.4) or pial (p = 0.4) location were not associated with LMD. The only factor predictive for LMD on univariate analysis was breast cancer histology (p = 0.002). Thirty-three percent (8 of 24) of breast cancer cavities developed LMD compared to 7% (10 of 137) other histology for a 1 year rate of LMD of 34% for breast versus 9% for non-breast histology. All LMD patients received WBI. Median survival following the diagnosis of LMD was 7 months (range 1-37 months). Patients treated with SRS targeting the post-operative cavity following resection of breast cancer metastases have a high risk of LMD in this series. Post-operative whole brain irradiation or novel strategies such as pre-operative SRS should be considered in this patient population.

Cerebrospinal Fluid Flow Cytometry Analysis in Newly Diagnosed Aggressive Non-Hodgkin Lymphomas at High Risk for Leptomeningeal Disease: Result of a Multicentric Prospective Italian Study.

Abstract 2919Poster Board II-895 Background:Flow cytometry (FCM) assessment of cerebrospinal fluid (CSF) has recently been known to increase the rate of positivity of occult leptomeningeal disease (LD) in comparison to conventional cytologic examination (CC). However it's still unknown its prognostic value. Patients and methods: The aim of this study was to compare CC vs FCM in a large cohort of patients with newly diagnosed aggressive NHL at high risk for LD (diffuse large B-cell lymphoma (DLBCL) IPI 2-3 and elevated LDH with at least two extranodal sites or with bone marrow, testis, paranasal sinuses, orbit or paravertebral involvement; Burkitt lymphoma (BL); blastoid variant of mantle cell lymphoma (B-MCL); B-cell precursor lymphoblastic lymphoma (B-LL); HIV+ aggressive lymphoma patients). All patients were required to have no evidence or signs of neurological disease. All patients received intrathecal standard prophylactic therapy with 12 mg of methothrexate except for BL that were given prophylaxis with 50 mg of liposomial aracytin for a total of 4 doses. CFS samples were analysed both with CC and FCM. The incidence of positive test for occult LD with FCM and CC was compared using the McNemar test for paired data. Results:Between August 2004 and June 2008, a total of 159 consecutive patients were enrolled in 11 Italian centres and underwent evaluation of CSF. Out of these, 128 patients (80%) were considered at high risk of occult LD. Clinical characteristics were: median age 53 years (IQR:43-62); DLBCL 96 patients (75%); BL 21 pts (16%); B-MCL 6 pts (5%); B-LL 5 pts (4%); 26 pts (20%) were HIV positive. FCM was able to detect a clonal population in 17 out of 128 patients (13%) whereas CC detected abnormal cells only among 7 pts (5%)(p= 0.0002). Therefore, 10 patients (8%) were discordant: FCM+/CC-. Among the 128 patients, there was no association between the CFS total protein, glucose level and the presence of positive analysis of FCM, whereas the difference between the number of WBC cells in CSF was significantly higher in patients with positive versus negative FCM with a median value of 12 cells/ul (IQR: 3.5;40) versus 1.0 cells/ul (IQR: 0.0;3.0) (p=0.0120). Univariate and multivariate analyses, using logistic models, showed that abnormal LDH (OR 3.98, 95%CI: 1-15.92)(p=0.05) and number of WBC cells in CSF ≥5 (OR 4.57, 95%CI:1.37-15.33)(p=0.014) were the only predictive factors of a positive test performed by FCM. From date of diagnosis, overall median follow up of survivors was 14 months (IQR:8-22). We observed 39 (30%) systemic progressions, 6 (5%) CNS progressions (in 5 cases an isolated CNS progression whereas 1 pts experienced a CNS along with systemic progression). Thirty-two (25%) patients died and causes of deaths were as follows: 27 progressive disease, 1 infection, 1 treatment related toxicity, 1 hepatitis, 2 unknown. PFS at 1 year was 71% (95%CI:62-78) in the whole group of patients. The progression risk was significantly higher in patients both FCM+/CC+ compared with patients both FCM-/CC- (1-yr PFS 43% vs 74%) (HR 3.8 95%CI:1.6-9.0) (p=0.003). An higher but not significant risk of progression was found in pts discordant (FCM+/CC-) with respect to patients both FCM-/CC- (1-yr PFS 65% vs 74%) (HR 1.61, 95%CI:0.63-4.11) (p=0.315). In the univariate and multivariate analyses performed with Cox models, we found that the presence of ECOG PS≥2 (HR 2.14, 95%CI: 1.14-4)(p=0.018) and level of protein in CSF >40/ul (HR 1.83 95%CI: 1.01-3.29)(p=0.045) were prognostic factor of PFS. Conclusion:FCM assessment of CSF increase the rate of positivity of occult LD compare with CC but it's clinical relevance is still to be clearly defined. Our preliminary data suggest that patients both FCM+/CC+ have an higher risk of progression compared with those both negative, whereas discordant cases may have an intermediate prognosis. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

COMPARATIVE RISK OF LEPTOMENINGEAL DISSEMINATION OF CANCER AFTER SURGERY OR STEREOTACTIC RADIOSURGERY FOR A SINGLE SUPRATENTORIAL SOLID TUMOR METASTASIS

To test the hypothesis that differential risks of developing leptomeningeal disease (LMD) exist in patients having a single supratentorial brain metastasis resected via a piecemeal or en bloc approach or treated with stereotactic radiosurgery (SRS). Between 1993 and 2006, 827 patients with a supratentorial brain metastasis underwent resection or SRS at The University of Texas M.D. Anderson Cancer Center. The primary outcome was the incidence of LMD. Resection was performed piecemeal in 191 patients and en bloc in 351 patients; 285 patients received SRS. LMD occurred in 33 patients, 29 in the resection group and 4 in the SRS group. Risk of LMD was significantly higher with piecemeal tumor resection than with other procedures (SRS: hazard ratio [HR] for piecemeal, 5.8; 95% confidence interval [CI], 1.9-17.2; P = 0.002; en bloc, HR for piecemeal, 2.7; 95% CI, 1.3-5.6; P = 0.009). The difference between piecemeal and en bloc was particularly pronounced in patients with a melanoma primary (HR, 8.4; 95% CI, 1.8-39.2; P = 0.007). The risk of LMD was not significantly different between en bloc resection and SRS (HR for en bloc, 2.1; 95% CI, 0.7-6.4; P = 0.21). Similar results were obtained when comparing effects of SRS and both resection approaches after limiting the sample to patients with tumors in a specific volume range. Piecemeal resection of a supratentorial brain metastasis carries a higher risk of LMD than en bloc resection or SRS. Further assessment of the role of the 2 surgical resection approaches and SRS in a controlled prospective setting with large numbers of patients is warranted.

Posterior Fossa Metastases: Risk of Leptomeningeal Disease When Treated with Stereotactic Radiosurgery Compared to Surgery

Leptomeningeal disease (LMD) represents a diffuse form of central nervous system metastatic disease that is often associated with poor quality of life and prognosis. Our objective was to compare the incidence of LMD in patients with posterior fossa metastases (PFM) following stereotactic radiosurgery (SRS) versus surgical resection. The medical records of 93 patients aged 57.9 +/- 10.8 years (mean +/- SD) with PFM treated at the Cleveland Clinic from 1995 to 2001 were analyzed retrospectively. Treatments consisted of surgery with whole brain radiation therapy (WBRT) or SRS with or without WBRT. The impact of age, Karnofsky performance status (KPS) at presentation, Radiation Therapy Oncology Group, recursive partitioning analysis (RPA) class, status of extracranial disease, number, size, volume, pathology of brain metastases and steroid use were studied using univariate and multivariate analyses. There were 80 evaluable patients (10 lost to follow-up and three excluded for supratentorial surgery with subsequent LMD). LMD occurred after the surgical removal of the PFM in 9 of 18 patients (50%), whereas LMD occurred after SRS in 4 of 62 patients (6.5%) (p = 0.0028). Multivariate analysis also showed that patients who had surgery were more likely to develop LMD compared to patients treated with SRS (p = 0.0024). Patients had a median KPS decline of 30 points after LMD was diagnosed. There was no statistically significant difference in survival of patients with LMD and the rest of the patients (13.5 vs. 11.7 months, p = 0.7659). Patients treated surgically had significantly larger lesions (3.43 +/- 0.74 vs. 1.96 +/- 0.95 cm maximum diameter, p < 0.0001). All surgical patients belonged to RPA class II at diagnosis. Their survival was not different from the RPA class II patients in the SRS group. Surgery and SRS had comparable complication rates (8.1% vs. 5.6%, p = 0.99), although the surgical complications were more serious (e.g. hemorrhage, CSF leak). The duration of steroid use was longer after SRS compared to surgery (2.1 +/- 3.6 vs. 1.3 +/- 2.4 months); however, the difference was not statistically significant. Myopathy and psychosis in one patient after SRS, were the only steroid-related complications. There was no statistically significant association between the primary tumor type and the presence of LMD. In this retrospective analysis of patients with PFM, SRS was associated with a lower incidence of LMD than was surgery. Although LMD was associated with rapid and considerable decline in the quality of life, it did not influence the overall survival. SRS was associated with less serious complications than surgery. Surgery in this study was performed on patients with larger lesion sizes and a trend toward poorer initial performance status, which could bias these results. A prospective study directly comparing surgery and SRS and further evaluating the significance of LMD in PFM is warranted.