Diagnosis Of Leptomeningeal Carcinomatosis Research Articles

Clinical features and outcomes of patients with breast cancer with leptomeningeal carcinomatosis.

e13162 Background: Leptomeningeal carcinomatosis (LMC) is a rare, but deadly complication in breast cancer, with prior studies showing median overall survival (OS) of 15 weeks. There is a paucity of data on histologic and receptor subtype-specific survival, and there is no standard of care currently for treatment of LMC in breast cancer. We reviewed the outcomes of a contemporary cohort of breast cancer patients (pts) with LMC. Methods: This is a single-institution retrospective analysis of 38 female breast cancer pts diagnosed with LMC between 2016-2023, based on radiographic features and/or positive cerebrospinal fluid (CSF) cytology or CSF circulating tumor cells (CTCs). Patients consented to share information with a research biorepository, and we conducted a chart review of their clinical features and OS with LMC. Results: 25 pts (65.8%) had invasive ductal carcinoma (IDC), 7 pts (18.4%) had invasive lobular carcinoma (ILC), 4 (10.5%) had metaplastic carcinoma, and 2 (5.3%) had mixed IDC/ILC. 22 pts (57.9%) had triple-negative breast cancer (TNBC), 12 (31.6%) had estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and 4 (10.5%) had HER2+ disease. Median age at LMC diagnosis was 50 years. Median time between Stage IV and LMC diagnosis was 11 months. Pts received a median of 2 lines of systemic therapy for metastatic disease prior to LMC diagnosis. 11 pts (28.9%) had parenchymal brain metastasis prior to LMC diagnosis. 32 pts (84.2%) had signs of LMC on Magnetic Resonance Imaging of the brain and/or spine at diagnosis. 25 pts underwent CSF cytology and 13 pts underwent CSF CTC evaluation at LMC diagnosis; 14/25 pts (56%) had positive CSF cytology and 10/13 pts (76.9%) had detectable CSF CTCs. 21 pts (55.3%) underwent whole-brain radiotherapy, and 2 pts (5.3%) received proton craniospinal irradiation. 21 pts (55.3%) received IT therapy. 27 pts (71.1%) received at least 1 line of systemic therapy post-LMC diagnosis. Median OS between LMC diagnosis and death or last oncology follow up for the entire cohort was 5 months (range 0-57 months, 95% CI 3.0-8.0). There was a significant difference in median OS with LMC by receptor subtype: TNBC 3.5 months, ER+/HER2- 8 months, and HER2+ 23 months (p=0.0047). Two HER2+ pts survived ≥ 3 years post-LMC diagnosis with anti-HER2 antibody-drug conjugates and tyrosine kinase inhibitors +/- stereotactic radiosurgery (SRS) to parenchymal brain metastases. Amongst 9 pts with ER+/HER2-low disease, longer survival with LMC (≥ 16 months) was observed with trastuzumab deruxtecan, IT topotecan +/- IT trastuzumab, and SRS to parenchymal brain metastases. Conclusions: This study highlights heterogeneity in outcomes amongst breast cancer pts with LMC by receptor subtype, as well as improvement in outcomes for selected pts treated with novel therapeutics and a multidisciplinary approach. Larger prospective studies are needed to inform treatment paradigms for LMC.

The importance of CSF neoplastic cell recognition in the diagnosis of leptomeningeal carcinomatosis

The importance of CSF neoplastic cell recognition in the diagnosis of leptomeningeal carcinomatosis

New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid.

Leptomeningeal carcinomatosis represents a terminal stage and is a devastating complication of cancer. Despite its high incidence, current diagnostic methods fail to accurately detect this condition in a timely manner. This failure to diagnose leads to the refusal of treatment and the absence of clinical trials, hampering the development of new therapy strategies. The use of liquid biopsy is revolutionizing the field of diagnostic oncology. The dynamic and non-invasive detection of tumor markers has enormous potential in cancer diagnostics and treatment. Leptomeningeal carcinomatosis is a conditionwhere invasive tissue biopsy is not part of the routine diagnostic analysis, making liquid biopsy an essential diagnostic tool. Several elements in cerebrospinal fluid (CSF) have been investigated as potential targets of liquid biopsy, including free circulating tumor cells, free circulating nucleic acids, proteins, exosomes, and even non-tumor cells as part of the dynamic tumor microenvironment. This review aims to summarize current breakthroughs in the research on liquid biopsy, including the latest breakthroughs in the identification of tumor cells and nucleic acids, and give an overview of future directions in the diagnosis of leptomeningeal carcinomatosis.

Treatment pattern and outcomes of leptomeningeal carcinomatosis in India – a retrospective study

Leptomeningeal carcinomatosis (LMC), the metastatic spread of cancer to the leptomeninges, is a rare complication and has a dismal prognosis. Due to limited data available on LMC from India, we conducted a country-wise audit of LMC across 15 centres in India. The current study conducted in 2020, was a retrospective, multicentric audit of adult patients (aged ≥18 years) with diagnosis of LMC and who received treatment during 2010-2020. Baseline characteristics, details related to previous treatments, cancer sites, LMC diagnosis, treatment pattern and overall survival (OS) were collected. Descriptive statistics were performed, and Kaplan Meier analysis was performed for the estimation of OS. Among the patients diagnosed with LMC (n=84), diagnosis was confirmed in 52 patients (61.9%) and 'probable' in 32 (38.1%) patients. The three most common cause of malignancy were non-small cell lung cancer (NSCLC), breast cancer and gastrointestinal cancer with 45 (53.6%), 22 (26.1%) and 9 (10.7%) patients respectively. Intrathecal therapy was offered in 33 patients (39.3%). The most common intrathecal agent was methotrexate in 23 patients (27.4%). The median OS was 90 days (95% CI 48-128). Among tested variables, intrathecal therapy administration (hazard ratio [HR]=0.36, 95% CI 0.19-0.68) and primary in lung (HR=0.43, 95% CI 0.23-0.83) had a favourable impact on OS. Prognosis with leptomeningeal carcinomatosis is poor with a significant burden of morbidity and mortality in India. This data aims to highlight the current outcomes and facilitate further research on LMC. None.

Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: A real-world analysis of outcomes, clinical and pathologic characteristics.

2029 Background: Brain metastasis (BM) and Leptomeningeal Carcinomatosis (LC) are uncommon complications in gastroesophageal carcinoma (GEC) patients (pts). These patients have a poor prognosis and are challenging to study. We described the clinicopathologic features and outcomes in the largest real-world cohort of CNS metastasis in GEC pts. Methods: We conducted a single-center retrospective study of GEC pts treated at the Princess Margaret Cancer Centre from 2007 to 2021 who developed BM. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of BM or LC diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used to examine the association of baseline covariates and survival. Results: Of 3283 consecutive pts with GEC, 101 (3.08%) were diagnosed with BM and 20 with LC (0.61%). Most pts with BM were male (75.3%), non-Asian (93%), with a primary gastroesophageal junction tumor (47%) and adenocarcinoma histology (86%). Among pts with known HER2 status (N= 48), 60% were HER2 positive (defined as IHC 3+ or IHC 2+/FISH+). All patients with LC had adenocarcinoma histology; most were signet-ring subtype (85%), poorly differentiated (80%) histology and only 15% (2/13) were HER2 positive. Median survival was 0.8; 3.8; and 7.7 months (mo) in BM pts treated with palliative care only, radiation only and surgery followed by radiation, respectively (p< 0.001). In LC, median survival was 0.7 mo in pts who had palliative care only (7/20) and 2.7 mo for those (13/20) who had whole brain radiation therapy (WBRT) (p .008). Multivariate analysis showed a higher probability of death in patients with number of BM ≥4 (p 0.02) and predicted superior survival in patients who received radiation and surgery followed by radiation (p 0.02). Conclusions: This is the most comprehensive summary of clinicopathologic characteristics and survival in patients with GEC and BM and LC disease to date. Biomarker analysis reveals an enriched frequency of HER2 expression in BM, while this is uncommon in pts with LC. BM pts who were treated with surgery followed by radiation had a significantly improved OS. WBRT benefited patients with LC over palliative care alone. These findings add to our understanding for the management of this understudied population with poor survival. [Table: see text]

Brain metastases from hepatopancreatobiliary malignancies

While colorectal and gastroesophageal cancer represent the two gastrointestinal (GI) tumor entities with the highest incidence of brain metastatic (BM) disease, data on the clinical course of BM patients from hepatopancreatobiliary malignancies are rare. Patients with cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC) and gastroenteropancreatic neuroendocrine neoplasms (GEP NEN). Treated for BM between 1991 and 2017 at an academic care center were included. Brain metastases-free survival (BMFS) was defined as interval from first diagnosis until BM development. Overall survival (OS) was defined as interval from diagnosis of BM until death or last date of follow-up. Outcome was correlated with clinical and treatment factors. 29 patients from overall 6102 patients (0.6%) included in the Vienna Brain Metastasis Registry presented with BM from hepatopancreatobiliary primaries including 9 (31.0%) with CCA, 10 (34.5%) with HCC, 7 (24.1%) with PDAC and 3 (10.3%) with GEP NEN as primary tumor. Median BMFS was 21, 12, 14 and 7 months and median OS 4, 4, 6 and 4 months, respectively. Karnofsky Performance Status (KPS) below 80% (p = 0.08), age above 60 years (p = 0.10) and leptomeningeal carcinomatosis (LC) (p = 0.09) diagnosed concomitant to solid BM showed an inverse association with median OS (Cox proportional hazards model). In this cohort of patients with BM from hepatopancreatobiliary tumor entities, prognosis was shown to be very limited. Performance status, age and diagnosis of LC were identified as negative prognostic factors.

Complete Cerebrospinal Fluid Response to T-DM1 in HER2 Positive Metastatic Breast Cancer: A Case Report

Leptomeningeal carcinomatosis is a rare but serious consequence of pre-existing tumors, such as breast, lung, and gastrointestinal carcinomas. Further, leptomeningeal carcinomatosis is more frequently diagnosed with breast cancers, if only because breast cancers are diagnosed far more often than any other carcinomas. In this paper, we present the case of a leptomeningeal carcinomatosis patient who experienced complete remission following therapy targeted at the Her-2 (human epidermal growth factor receptor 2-positive) receptor. This patient's diagnosis was complicated by the fact that brain and column MRI imaging were clear, but analysis of the cerebrospinal fluid led to the conclusion of leptomeningeal carcinomatosis. The tests were requested because the patient, under chemotherapy for advanced breast cancer at the time, reported some neurological symptoms. Following the diagnosis of leptomeningeal carcinomatosis and subsequent T-DM1 Her-2 receptor therapy, the patient showed a complete response to leptomeningeal carcinomatosis within 30 days and survived for another 16 months. This case offers compelling evidence that the effect TDM1 Her-2 receptor therapy has on a patient's remission and long-term survivability is considerably better than other therapies for similar pre-existing conditions diagnosed with leptomeningeal carcinomatosis. Further prospective studies should confirm these findings.

Association of intrathecal trastuzumab to standard therapy in patients with leptomeningeal metastasis in HER2 positive breast cancer.

e13021 Background: Leptomeningeal metastases are rare but fatal manifestation of metastatic breast cancer, especially in HER2 positive sub-type, with limited treatment options and median overall survival in the range of only 4-6 weeks in untreated patients. Methods: Our prospective study included 9 patients with HER2 positive breast cancer with leptomeningeal metastases that received intrathecal treatment with Trastuzumab along with systemic therapy. Data was compared with a control lot of 9 patients with leptomeningeal metastasis that did not receive intrathecal treatment. Radiotherapy was administered in all patients. The patients included in the study received cures of 150 mg of Trastuzumab injected intrathecal every 3 weeks. Results: Median age of the patients at the time of diagnosis was 53 years. Median time from diagnosis of BC until diagnosis of leptomeningeal carcinomatosis was 3.4 years. Median progression free survival for patients receiving trastuzumab intrathecal was 11.1 months compare with 6.4 months in patients receiving standard treatment, p < 0.019. In our lot of patients, response rate was 66.6%. A clinical benefit with symptoms relief was observed in 77.7% of patients. Mean number of administrations was 12. Two patients presented pain and in two instance the administration was not possible. Concurrent systemic treatment consisted in lapatinib and capecitabine (22.2%), trastuzumab emtansine (44.5%), tucatinib combination (22.2%), vinorelbine (11.1%) and no unexpected toxicity to systemic treatment was noticed. Conclusions: Intrathecal administration of trastuzumab along with systemic treatment and radiotherapy, might improve or stabilise the consequences of leptomeningeal involvement by HER2-positive breast cancer with manageable toxicity.

Leptomeningeal carcinomatosis: Retrospective review of a large series.

e14005 Background: Leptomeningeal carcinomatosis (LMC) remains associated with a poor outcome and effective treatment options are not currently available. Knowledge about risk factors, diagnosis and optimal treatment of LMC is still limited. Methods: We performed a retrospective analysis of all consecutive patients with a solid tumor and LMC confirmed by CSF (cerebrospinal fluid)-positive cytology, diagnosed at our institution between January 2013 and November 2020. Clinical, imaging and cytologic data were collected. We used multivariable Cox regression models adjusted for age and Eastern Cooperative Oncology Group (ECOG) performance status to test the prognostic impact of clinical and treatment-related variables. Results: A total of 73 patients with LMC were identified, 75% female. The most common cancers were breast (51%, n = 37), lung (22%, n = 16), and melanoma (11%, n = 8). Most patients presented with intracranial hypertension (58%, n = 42), followed by cerebellar symptoms (20%, n = 15), radiculopathy (19%, n = 14), cranial nerve palsies (16%, n = 12), seizures (12%, n = 9), and other (4%, n = 3). More than half of patients (56%) had evidence of leptomeningeal involvement only, while 25% of patients (n = 18) had known central nervous system (CNS) metastases and 19% (n = 14) were diagnosed simultaneously with CNS metastases. Median time from primary tumor diagnosis to LMC was 32 months. Median overall survival (mOS) was 1.57 months (95% CI 1.17-2.32 months), with 15% of patients alive at 6 months (95% CI 9-26%). Patients with gynecological (7%, n = 5) and lung cancer had the best mOS (67 and 64 days, respectively), and patients with melanoma had the worst mOS (18 days). mOS in patients with evidence of meningeal involvement by MRI was 41 days, compared to 71.5 days in patients with a negative MRI. Starting a new systemic treatment was associated with a better prognosis (survival hazard ratio (HR) 0.39, 95% CI 0.21-0.75, p = 0.004). Forty patients (55%) received specific treatment for LMC. Neither intrathecal treatment nor radiation were associated with an improved outcome (HR 1.03, 95% CI 0.51-2.10, p = 0.930 and HR 0.60, 95% CI 0.30-1.17, p = 0.130, respectively). Presenting with seizures was significantly associated with a worse prognosis (HR 3.23, 95% CI 1.35-7.76, p = 0.009). In CSF cytology, both pleocytosis (> 5 cells/mm3) and hyperproteinorhachia were individually associated with a worse prognosis (pleocytosis: HR 1.94, 95% CI 1.16-3.26, p = 0.012; hyperproteinorhachia: HR 2.61, 95% CI 1.28-5.32, p = 0.008). Conclusions: In this large series of patients diagnosed with LMC based on positive CSF cytology, the outcome was poor. Absence of leptomeningeal involvement by MRI and switching to a new treatment regimen were associated with a better outcome, likely reflecting tumor burden and patient selection. LMC will likely become more common as systemic treatment options and imaging improve and effective treatment options are an urgent and yet unmet need.

Leptomeningeal carcinomatosis and breast cancer: a systematic review of current evidence on diagnosis, treatment and prognosis.

Leptomeningeal carcinomatosis (LC) is a rare but challenging manifestation of advanced breast cancer with a severe impact on morbidity and mortality. We performed a systematic review of the evidence published over the last two decades, focusing on recent advances in the diagnostic and therapeutic options of LC. Lobular histology and a triple-negative intrinsic subtype are well-known risk factors for LC. Clinical manifestations are diverse and often aspecific. There is no gold standard for LC diagnosis: MRI and cerebrospinal fluid cytology are the most frequently used modalities despite the low accuracy. Current standard of care involves a multimodal strategy including systemic and intrathecal chemotherapy in combination with brain radiotherapy. Intrathecal chemotherapy has been widely used through the years despite the lack of data from randomized controlled trials and conflicting evidence on patient outcomes. No specific chemotherapeutic agent has shown superiority over others for both intrathecal and systemic treatment. Although endocrine therapy was heuristically considered unable to exert significant control on central nervous system metastatic disease, retrospective data suggest a favourable toxicity profile and even a possible positive impact on survival. In recent years, encouraging data on the use of targeted agents has emerged but further research in this field is required. Palliative treatment in the form of whole brain or stereotactic radiotherapy is associated with improvement in clinical manifestations and quality of life, with no proven impact on survival. The most investigated prognostic factors include performance status, non-triple-negative disease and multimodal treatment. Validation of prognostic scores is necessary to aid clinicians in the identification of patient subgroups that are most likely to benefit from an intensive therapeutic approach.

LMD-15. Beyond cytologY - A single institution experience using CNSideTM for diagnosing and monitoring treatment response in Non-Small Cell Lung Cancer patients with Leptomeningeal Carcinomatosis (LMC)

IntroductionLeptomeningeal Carcinomatosis (LMC) occurs in 3–9% of Non-Small Cell Lung Cancer (NSCLC) patients. Diagnosis of LMC includes clinical evaluation, imaging, and cytology. These have modest sensitivity and are inadequate for monitoring treatment response. Biocept’s CNSideTM is a proprietary assay utilizing a 10-antibody capture cocktail with microfluidic chamber that quantitatively detects tumor cells in the cerebrospinal fluid (CSF). Switch BlockerTM is a proprietary single gene assay that detects actionable mutations in the CSF. We describe a retrospective single institution experience using these assays in NSCLC patients with confirmed LMC or suspected LMC, treated between 2017 and 2021.MethodsFor fresh samples, CNSide and cytology were used to detect tumor cells, NGS and Switch Blocker was used to detect actionable mutations. Frozen samples were analyzed by NGS and/or Switch Blocker assays.ResultsCSF was collected from 30 samples (16 unique patients), of which frozen (8 unique patients) and fresh samples (8 unique patients; 5 with and 3 without LMC). CNSide detected tumor cells in 100% samples (10/10) vs cytology in 40% samples (4/10). Of those without LMC, neither CNSide nor cytology identified tumor cells. In patients with serial samples, CNSide tracked the clinical course. Analysis of frozen CSF by NGS identified mutations including EGFR in six (6), ALK in three (3) and BRAF in one (1) patient, which correlated with the primary tumor. The median survival from diagnosis of LMC for those with frozen samples was 71.6 weeks.ConclusionWe demonstrate that 1) survival of patients with LMC can be prolonged, especially when an actionable target is identified, 2) CNSide has greater sensitivity in detecting LMC than cytology, and 3) quantitative monitoring of CSF tumor cells can be used to guide initial and subsequent therapies. Larger clinical trials are needed to better establish the utility of CNSide in managing LMC.

Treatment pattern and outcomes of leptomeningeal carcinomatosis in India: CRSF201901 study.

e14012 Background: Leptomeningeal carcinomatosis (LCM) is a rare event and has a dismal prognosis. Limited data is available from India on LCM. Hence we did this country wise audit of LCM. Methods: This was a retrospective, multicentric audit of adult (age ≥ 18 years) patients with diagnosis of LCM, conducted across India in 2020 for patients treated from 2010 to 2020. Baseline characteristics, previous treatments, cancer sites, LCM diagnosis details, treatment pattern and overall survival (OS) were collected. Descriptive statistics were performed and Kaplan Meier analysis was performed for estimation of OS. Results: We had 84 patients diagnosed with LCM. The diagnosis of LCM was confirmed in 52 (61.9%) and probable 32 (38.1%) patients. The mean age was 51.8 years (SD-10.8) and we had 46 (54.8%) females. The three most common site of malignancy were lung, breast and gastrointestinal with 45 (53.6%), 22 (26.1%) and 9 (10.7%) patients. The ECOG PS at the presentation of LCM was 1, 2 in and 3-4 in 41 (48.8%), 28 (33.3%) and 15 (17.9%) respectively. LCM was seen at diagnosis in 2 patients (2.4%) and at progression in rest. The status of the extracranial disease at the occurrence of LCM was progressive disease in 39 patients (46.1%). The treatment offered was best supportive care in 24 patients (28.6%), systemic therapy only in 27(32.1%), systemic therapy and intrathecal therapy in 22 (26.2%) and only intrathecal therapy in 11(13.1%). Among 33(39.3%) patients receiving IT methotrexate was used in 23 (27.4%) and the combination of methotrexate, AraC and hydrocortisone was used in 10 (11.9%). The CSF clearance rate was assessed in 24 (28.6%) patients and the clearance rate was 13.1% (n=11). The median duration of therapy was 4 weeks (IQR 1-14). The median os was 90 days (95% CI 46.2-133.8). Conclusions: LCM has a grave prognosis and nearly 1/3rd patients are treated with best supportive care. Intrathecal therapy though part of all guidelines is administered in 39% of patients. This data can serve as a benchmark for further improvement to facilitate studies for further improving the outcomes.

Abstract P2-20-07: Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience

Abstract Background Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein metastatic disease invades the meninges of the central nervous system via contiguous spread from bone or brain metastases or hematogenous spread from systemic disease. Breast cancer is the most common solid tumor etiology of LMC. Approximately 5% of patients (pts) with breast cancer develop LMC. LMC has a median survival of 4 weeks when untreated and 8-16 weeks with treatment. The diagnosis of LMC remains challenging with only 60% of pts having cerebrospinal fluid (CSF) positive for malignant cells. There is no generally accepted standard of care for treatment of LMC but it may involve intrathecal or systemic chemotherapy, whole brain or spinal radiotherapy, or a combination of modalities. We aimed to assess detection and treatment strategies of LMC in pts with breast cancer treated at the Ohio State University Comprehensive Cancer Center-James (OSUCCC-James) to better characterize the disease and guide clinical care. Methods An IRB-approved single-institution retrospective protocol was developed. Medical records of 469 pts who had undergone a procedure related to LMC diagnosis or treatment were identified and reviewed to determine study eligibility. Comprehensive data was obtained through information warehouse and chart review was performed for the eligible 69 pts with breast cancer diagnosed with LMC and treated at the OSUCCC-James between January 1, 2005 and December 31, 2015. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan Meier methods. Comparisons in OS between groups were analyzed using Log-rank tests. Results Sixty-nine female pts were included in the analysis with the following characteristics: median age 55.7 years (range: 48-60.6 years), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (86%; N=59), and Caucasian (78%; N=54). They had the following subtypes hormone receptor positive (HR +), and human epidermal growth factor receptor (HER2) negative (61%, N=42), triple negative (25%, N=17) and HER2 positive (10%, N=7). The most common sites of metastases included bone (42%), brain (28%), and lung (12%). The median time between the diagnosis of first metastasis and LMC was 0.9 years (range: 0-3.2 years). Of the 40 (58%) pts who underwent lumbar puncture, 21 (52%) pts had positive CSF cytology. Sixty-eight pts (99%) had MRI findings suggestive of LMC. The most common treatment modalities were systemic chemotherapy (N=14, 41%), radiotherapy (N=12, 35%), and intrathecal chemotherapy (N=14, 35%). Fifty-six pts (81%) had a change in systemic chemotherapy agent after diagnosis. The median OS of all pts was 2.4 months (95% confidence interval: 1.2-4.4). Pts with ER+/PR+/HER2- had a better OS (4.4 months, 95%CI 1.5, 6.1)) compared to those with HER2+ (1.3 months, 95%CI 0.2, 1.9) or ER-/PR-/HER2- (0.6 months, 95%CI 0.0, 15.8) subtypes (p-value=0.004). Pts with negative CSF cytology had a greater OS compared to those with positive CSF cytology (9.8 vs. 0.7 months, p=0.026) and pts who had a change in systemic treatment had a greater OS compared with patients who had no new treatment (2.5 months vs. 1.2 months, p =0.039). No significant difference was seen in OS between ECOG performance status groups. Conclusions LMC is a relatively rare yet devastating complication of breast cancer. Based on our institutional experience, LMC remains a clinical challenge and is associated with poor OS. Pts with triple negative and HER2 positive disease and those with high disease burden fare worse. Pts who had change in systemic therapy fare better. Dedicated clinical trials are urgently needed to improve outcomes. Citation Format: Hannah Rinehardt, Nicole Williams, Evan Morgan, Mahmooud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Vinay Puduvalli, Pierre Giglio, Maryam Lustberg, Robert Wesolowski, Sagar Sardesai, Daniel Stover, Jeffrey VanDeusen, Jose Bazan, Bhuvaneswari Ramswamy, Anne Noonan. Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-07.

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor.

BackgroundWe investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT) chemotherapy in patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.MethodsUsing clinical research data from the Asan Medical Center, we retrospectively analyzed data of patients diagnosed with LMC, confirmed via cerebrospinal fluid (CSF) analysis from January 2008 to December 2017.ResultsWe identified 1189 patients with lung adenocarcinoma harboring EGFR mutations. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8–23.6) months from the initial lung cancer diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastasis to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. Median survival duration from LMC diagnosis was 3.8 (IQR 1.5–8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of Ommaya reservoir (HR 0.445, P = 0.005) were associated with longer survival. EGFR‐tyrosine kinase inhibitor (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion.ConclusionsYounger age, initial diagnosis of metastatic disease, and metastasis to the brain or different lobes were associated with LMC in patients with EGFR‐mutant lung adenocarcinoma. Therapeutic interventions including EGFR‐TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes.Key pointsAge and disease status were associated with LMC in patients with EGFR‐mutant adenocarcinoma, and EGFR‐TKI, Ommaya reservoir, and good performance status were related to survival benefit.

MA13.03 Retrospective Study of Intrathecal Therapy for Non-Small Cell Lung Cancer (NSCLC) Patients with Leptomeningeal Carcinomatosis

Leptomeningeal carcinomatosis (LMC) is a devastating cancer-related neurological complication with poor prognosis. In EGFR-mutant (mut) NSCLC patients (pts), osimertinib achieves high penetration into cerebral-spinal fluid (CSF) and promising efficacy. However, for EGFR-mut T790M-negative pts treated with prior 1st- and 2nd-generation tyrosine kinase inhibitors (TKI) and for driver negative NSCLC pts, a combination of intrathecal therapy (IT) and systemic therapy (ST) seems to be an appropriate approach. Our purpose is to explore the clinical outcome of IT combined with ST among NSCLC with LMC depending on EGFR status. NSCLC pts with LMC treated with IT in our institution between 2010 and 2018 were retrospectively studied. After LMC diagnosis, intrathecal methotrexate (scheduled: 12mg twice weekly for 4 weeks, then 12mg weekly for 4 weeks) was given in combination with ST. A Kaplan-Meier survival analysis was performed for overall survival (OS) and progression free survival (PFS). A total of 39 pts were included. Patient’s clinical characteristics are summarized in table 1. EGFR status was 17 mut (del19: 11pts); 11 wild-type (wt) and 11 unknown (unk). LMC and NSCLC diagnosis were more likely to be synchronous in EGFR wt compared with EGFR mut. The median follow-up from LCM diagnosis was 10.2 months. At the time of this analysis, only 6 pts were alive. Thirty-two pts received ST in combination with IT, 18 (46%) pts chemotherapy (6wt/ 3mut/ 9unk), while 14 (36%) pts an EGFR TKI (1wt/ 13mut). Clinical response (improvement of neurological symptoms and/or KPS) was seen in 11 (65%) EGFR mut pts vs 2 (18%) wt pts (p=0.033). Median OS and PFS for the whole cohort were 23 weeks (95%CI, 8.1 to 37.9) and 10 weeks (95%CI, 7.1 to 12.8) respectively. Median OS was higher for EGFR mut pts compared to wt pts, 38 weeks (95%IC 13.6-62.4) and 19 weeks (95%IC, 4.06-33.9) respectively, however this difference was not statistically significant (p=0.36) probably due to lack of statistical power. Methotrexate-based IT given concurrently with systemic TKI may confer a higher clinical benefit and a trend toward OS benefit in NSCLC patients with LCM and EGFR activating mutations.

LPTO-10. ASSESSMENT OF LEPTOMENINGEAL CARCINOMATOSIS DIAGNOSIS AND OUTCOMES FROM 2005 TO 2015 AT THE OHIO STATE UNIVERSITY

BACKGROUND: Leptomeningeal carcinomatosis (LMC) is a complication of solid tumor malignancies where tumors metastasize to the leptomeninges. LMC complicates 4–15% of malignancies with incidence increasing as survival of patients with advanced cancer improves. Diagnostic methods include magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology. We assessed detection methods, incidence, and outcomes of LMC at The Ohio State University Comprehensive Cancer Center from 2005–2015. METHODS: This was a single-institution retrospective study of 160 patients with confirmed diagnosis of LMC. Patients with hematologic and central nervous system malignancies were excluded. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan-Meier methods. RESULTS: Median age of LMC diagnosis was 55.8 years (range: 48, 62.5). 69 (43%) patients had primary breast cancer, 41 (26%) had lung cancer, and 17 (11%) had melanoma. 73 patients (46%) presented with stage IV disease at initial diagnosis of the primary cancer, 41 (26%) with stage III disease, and 26 (16%) with stage II disease. Median time from diagnosis of primary cancer to diagnosis of LMC was 2 years (range: 0, 31.2). 158 (99%) patients had metastases at the time of LMC diagnosis, predominantly in bone (36%) or brain (36%). Median OS was 1.9 months (CI: 1.3, 2.5). 160 (100%) patients had an MRI of the brain or spine and 155 (97%) had MRI findings consistent with LMC. 75 (47%) patients underwent lumbar puncture, and 39 (52%) had CSF cytology positive for malignancy. CONCLUSIONS: Despite treatment, prognosis remains poor and confirmation of diagnosis can be challenging. This study highlights the need for novel therapeutics and improved diagnostic techniques for patients with LMC.

Assessment of Leptomeningeal Carcinomatosis Diagnosis and Outcomes from 2005 to 2015 at Ohio State University.

e13554 Background: Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein primary tumors metastasize to the leptomeninges surrounding brain and spinal cord. LMC complicates 4-15% of malignant solid tumors with incidence increasing as survival of patients with advanced cancer improves. Diagnostic methods include magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology. MRI findings may be nonspecific, and the gold standard of diagnosis is malignant cytology on CSF analysis. We assessed detection methods, incidence, and outcomes of LMC at The Ohio State University Comprehensive Cancer Center from 2005-2015. Methods: This was an IRB-approved single-institution retrospective study of 160 patients with confirmed diagnosis of LMC who were treated at the OSUCCC-James between Jan 1, 2005 and Dec 31, 2015. Patients with hematologic and central nervous system malignancies were excluded. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan-Meier methods. Results: Median age of LMC diagnosis was 55.8 years (range: 48, 62.5). 69 (43%) patients had primary breast cancer, 41 (26%) had lung cancer, and 17 (11%) had melanoma. 73 patients (46%) presented with stage IV disease at initial diagnosis of the primary cancer, 41 (26%) with stage III disease, and 26 (16%) with stage II disease. Median time from diagnosis of primary cancer to diagnosis of LMC was 2 years (range: 0, 31.2). 158 (99%) patients had metastases at the time of LMC diagnosis, predominantly in bone (36%) or brain (36%). Median OS was 1.9 months (CI: 1.3, 2.5). 160 (100%) patients had an MRI of the brain or spine and 155 (97%) had MRI findings consistent with LMC. 75 (47%) patients underwent lumbar puncture, and 39 (52%) had CSF cytology positive for malignancy. Conclusions: Patients with LMC commonly presented with stage IV breast cancer, lung cancer, or melanoma with metastases to the brain or bone. Despite treatment, prognosis remains poor and confirmation of diagnosis can be challenging. Clinicians should have a low threshold for investigating LMC in high risk patients presenting with neurologic signs or symptoms.

Association of MRI findings with clinical characteristics and prognosis in patients with leptomeningeal carcinomatosis from non-small cell lung cancer.

Magnetic resonance imagining (MRI) is helpful for diagnosis of leptomeningeal carcinomatosis (LMC) and localizing LMC symptoms. Goal of this study is how MRI findings of LMC are associated with clinical characteristics or prognosis in patients with non-small cell lung cancer (NSCLC). We retrospectively collected data on 283 patients with LMC from NSCLC, adenocarcinoma based on cerebrospinal fluid cytology. All patients had brain MRI with gadolinium enhancement at LMC diagnosis, and spinal MRI was performed at the physician's discretion. We evaluated the prognostic factors for overall survival (OS) of all patients and subgroup of patients with central nervous system cause of death. Two-hundred sixteen patients (76%) had definite or suggestive LMC findings and 67 had negative findings on brain MRI. Of the 37 patients who presented with cauda equina syndrome, 35 (95%) exhibited typical spinal MRI findings. Median OS of all patients was 3.65months (95% confidence interval, 3.06-4.18). There was no significant difference in median OS between MRI-negative and MRI-positive groups (4.31 vs. 3.48months, p = 0.711), whereas negative MRI finding showed longer median OS significantly in a subgroup of 77 patients with a central nervous system cause of death (p = 0.035). Considering clinical characteristics, progressive systemic disease, and altered mentality were significant prognostic factors associated with poor OS, whereas presenting symptom of headache with nausea/vomiting, intra-CSF chemotherapy, WBRT after LMC diagnosis, and concurrent RTKi treatment were significant for favorable OS in multivariable analysis. Positive MRI findings suggests heavier disease burden than negative MRI findings in patients with LMC who died of a central nervous system cause. Spinal MRI findings in patients with LMC correlate with cauda equina symptoms.

Palliative Radiotherapy for Leptomeningeal Carcinomatosis-Analysis of Outcome, Prognostic Factors, and Symptom Response.

Introduction: The purpose of this article is to report our institution's 10-year experience on palliative radiotherapy for the treatment of leptomeningeal carcinomatosis (LC), assessing survival, neurologic outcome, and prognostic factors.Patients and methods: We retrospectively analyzed 110 patients who received palliative radiotherapy for LC between 2008 and 2018. The most common histologies were breast cancer (n = 43, 39.1%) and non-small cell lung cancer (NSCLC) (n = 31, 28.2%). Radiotherapy was administered as whole-brain radiotherapy (WBRT) (n = 51, 46.4%), focal spinal RT (n = 11, 10.0%) or both (n = 47, 42.7%). Twenty-five patients (22.7%) were selected for craniospinal irradiation. Clinical performance and neurologic function were quantified on the neurologic function scale (NFS) before and in response to therapy. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for survival.Results: Ninety-eight patients (89.1%) died and 12 (10.9%) were alive at the time of analysis. Median OS from LC diagnosis and from the beginning of RT was 13.9 weeks (IQR: 7.1–34.0) and 9.9 weeks (IQR: 5.3–26.3), respectively. In univariate analysis, prognostic of longer OS were a Karnofsky performance scale index (KPI) of ≥70% (HR 0.20, 95%-CI: [0.13; 0.32], p < 0.001), initially moderate neurological deficits (NFS ≤2) (HR 0.32, 95% CI: [0.19; 0.52], p < 0.001), symptom response to RT (HR 0.41, 95%-CI: [0.26; 0.67], p < 0.001) and the administration of systemic therapy (HR 0.51, 95%-CI: [0.33; 0.78], p = 0.002). Prognostic of inferior OS were high-grade myelosuppression (HR 1.78, 95% CI: [1.06; 3.00], p = 0.03) and serum LDH levels >500 U/l (HR 3.62, 95% CI: [1.76; 7.44], p < 0.001). Clinical performance, symptom response and serum LDH stayed independently prognostic for survival in multivariate analysis. RT was well-tolerated and except for grade III myelosuppression in 19 cases (17.3%), no high-grade acute toxicities were observed. Neurologic symptom stabilization was achieved in 83 cases (75.5%) and a sizeable improvement in 39 cases (35.5%).Conclusion: Radiotherapy is a well-tolerated and efficacious means of providing symptom palliation for patients with LC, delaying neurologic deterioration while probably not directly influencing survival. Prognostic factors such as clinical performance, neurologic response and serum LDH can be used for patient stratification to facilitate treatment decisions.

&lt;p&gt;Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis&lt;/p&gt;

BackgroundLeptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC.Patients and methodsTwenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0–2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.ResultsTwenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein <100 mg/dL (P=0.018) and no more than mild or moderate neurologic deficits (NFS ≤2; P=0.007) were predictive of longer OS. So were the neurologic response to treatment (P=0.018) and the application of systemic therapy after RT completion (P=0.029). The presence of CSF flow obstruction was predictive of shorter OS (P=0.026). In multivariate analysis, age at LC diagnosis (P=0.018), KPI (P<0.001) and neurologic response (P=0.037) remained as independent prognostic factors for longer OS. Treatment-associated toxicity was manageable and mostly grades I and II according to the Common Terminology Criteria for Adverse Events v4.0. Eight patients (32%) developed grade III myelosuppression. Neurologic symptom stabilization could be achieved in 40.0% and a sizeable improvement in 28.0% of all patients.ConclusionCSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options.