Cause of mortality in patients with lung cancer and brain metastasis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21743-e21743
Author(s):  
Rajat Thawani ◽  
Kareem Fakhoury ◽  
Kevin Douglas Becker
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Cause Of Death ◽  
Cancer Progression ◽  
Systemic Disease ◽  
Brain Lesion ◽  
Eastern Cooperative Oncology Group ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Group Status

e21743 Background: Lung cancer is the most common cause of cancer-related mortality and most deaths are associated with metastatic disease, with brain being a common site. Historically, whole brain radiation therapy was the treatment of choice and resulted in median survivals in the range of 6 months. There is no consensus in management of patients who have brain metastasis with systemic disease.We aim to evaluate patients with brain metastasis from lung cancer for cause of death, to investigate whether patients died from central nervous system (CNS) progression or systemic disease or other/undetermined causes. Our hypothesis is that most deaths in contemporary patients with brain metastasis in lung cancer are due to systemic disease, and less commonly due to CNS progression. Methods: In this retrospective observational study, we did a chart review of all adult patients with non-small cell lung cancer and brain metastasis or leptomeningeal disease, who received treatment at Maimonides Cancer Center between 2010 and 2017. Patients with unavailable or incomplete medical records were excluded. Baseline characteristics, pathological factors of the tumor and cause of death was collected from the chart. The cause of death was categorized into systemic and brain causes, and difference in characteristics of patients and tumor were studied. Results: A total of 132 patients were included and their charts were reviewed. Out of 132, 96 could have a clear cause of death categorized into systemic or brain causes, the rest were either mixed or uncategorized. We found that 33% patients died of brain metastasis, and related causes, whereas 67% died of systemic disease progression. There were no different in the two groups in terms of gender, smoking status, histology, size of lung lesion, or number and size of brain lesion. The patients who died of brain metastasis had a significantly higher age, and worse Eastern Cooperative Oncology Group status. Interestingly, the patients who died of systemic causes more commonly had adrenal metastasis (12 vs 0) which was statistically significant, and liver (14 vs 3) metastasis which was not statistically significant. Conclusions: Two-thirds of patients with brain metastases died of systemic disease rather than CNS progression. This may reflect improvements in systemic and local therapies to forestall cancer progression in the CNS. This finding suggests that delaying systemic therapy for CNS treatment may negatively impact overall cancer control. More research needs to be done to answer this question with certainty, including prospective clinical trials.

scholarly journals CMET-34. IMPROVEMENT OF LEPTOMENINGEAL DISEASE FOLLOWING INFECTIOUS MENINGITIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi59-vi59 ◽  
Author(s):  
Nicholas Metrus ◽  
Carolos Kamiya ◽  
Shiao-Pei Weathers ◽  
Christa Seligman ◽  
Barbara O’Brien
Keyword(s):  
Median Survival ◽  
Post Infection ◽  
Systemic Disease ◽  
Cancer Center ◽  
Cns Infection ◽  
Leptomeningeal Disease ◽  
History Of ◽  
Md Anderson ◽  
To Receive ◽  
Systemic Therapies

Abstract INTRODUCTION The incidence of leptomeningeal disease (LMD) is increasing, due to better imaging, earlier diagnosis and improved systemic disease control. However, many of the systemic therapies do not cross the blood brain barrier (BBB) and, despite treatment with radiation and/or intrathecal (IT) chemotherapy, median survival is approximately 4-6months in solid tumors complicated by LMD. Repeated IT injections increase the risk of CNS infection. Preclinical models have shown that infectious meningitis transiently modifies the BBB. METHODS Our series consisted of 6 LMD patients (5 breast cancer primary, 1 lung cancer primary) treated on IT chemotherapy at MD Anderson Cancer Center between 2013 and 2018, who subsequently developed infectious meningitis. Three patients had history of parenchymal metastases in addition to LMD and four had history of radiation to brain and/or spine. LMD was confirmed by cytology and/or imaging. All were treated with IT topotecan. RESULTS CSF cultures were positive for Proprionobacterium acnes in three patients, Pseudomonas aeruginosa in two, and Raoultella ornithinolytica in one, who died shortly thereafter. Antibiotic regimens were variable. Three patients went on to receive IT chemotherapy post-infection (two never discontinued IT chemotherapy throughout infection). Those that had IT chemotherapy post-infection cleared CSF and imaging findings of LMD or maintained stability of radiographic LMD burden until death. No patients died directly from LMD. One patient, who developed infection after Ommaya placement and was never initiated on IT chemotherapy, still cleared his CSF of malignant cells. Excluding the patient who died shortly after meningitis diagnosis, the average time from meningitis diagnosis to death was 8.8 months and the average median survival from LMD diagnosis to death was 14 months. CONCLUSION Our findings support further evaluating the safety and timing of IT chemotherapy with active infectious meningitis and the potential synergistic benefit of increased immunogenicity and chemotherapy in LMD.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Type ◽  
Primary Cancer ◽  
Extracranial Metastases ◽  
The Brain

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Single center, open and prospective evaluation of genomic sequencing on cerebro-spinal fluid, brain metastatic lesions and plasma from patients in non-small cell lung cancer with brain metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13578-e13578
Author(s):  
Chunhua Ma ◽  
Chuoji Huang ◽  
Zhi Li ◽  
Rong Jiang ◽  
Juncheng Zhang
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Primary Tumor ◽  
Brain Lesion ◽  
Gene Mutations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients

e13578 Background: Leptomeningeal metastases are observed in 9.4% non–small Cell Lung Cancer (NSCLC) patients with EGFR mutations. Depending on patient specific gene mutations, tumor cells may also have different proliferative activity, leading to differential metastatic potential. However, the clinical significance of observed gene mutation differences between CSF, plasma, primary pulmonary tumor and metastatic brain tumor samples remains unclear and should be further explored. Methods: From Apr. 2018 to Jan. 2019, plasma and CSF paired samples were drawn from consented NSCLC patients with diagnosed brain metastasis. Of these 21, brain lesion samples were obtained from 5 patients. All the samples were tested by next-generation sequencing. Patients were treated based on the detection results. Results: For this cohort, the detection rate of EGFR mutations in CSF cfDNA versus plasma cfDNA/CTC was 57.1% and 23.8% respectively (p < 0.05). For patients who had not received tyrosine kinase inhibitor (TKI) therapy, the CSF cfDNA EGFR mutation results were consistent with results for plasma, brain lesion and primary tumor samples. Conversely, for patients who had received TKI therapy, EGFR mutations detected in CSF were consistent with those from brain samples, but different from those observed in plasma or primary tumor samples. A high response rate (ORR, 70%; DCR, 90%) was observed in patients with EGFR positive detected in CSF after treatment with second orthird-generation TKI. Among the EGFR mutations detected in CSF, the EGFR uncommon mutation frequency was 58.3%(7/12), including G7I9A/L861Q/L703P/R776H/G575R/T790M 85.7% (6/7) of these occurred in LM patients. One patient who progressed from BM to LM had an uncommon mutation in the CSF sample. Among these five patients with EGFR G719A or L861Q positive and T790M negative, 4 patients had PR and 1 patient had SD after the second-generation TKI therapy. Conclusions: Differences in EGFR gene mutations were observed between CSF, plasma, primary pulmonary lesion and brain tissue samples in NSCLC patients with diagnosed brain metastasis after TKI therapy. The reasons for this discrepancy remain to be understood. Nevertheless, CSF may be a useful prognostic tool for patient monitoring and metastasis risk evaluation. The detection of uncommon EGFR mutations may increase the risk of LM in NSCLC patients. Clinical trial information: ChiCTR1800017499.

Standard-Dose Osimertinib in EGFR-Mutated Non–Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease

2021 ◽  
pp. 561-568
Author(s):  
Luke S. McLean ◽  
Wasek Faisal ◽  
Sagun Parakh ◽  
Steven C. Kao ◽  
Craig R. Lewis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Median Overall Survival ◽  
Treatment Options ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Leptomeningeal Disease ◽  
Small Cell Lung ◽  
Egfr Mutated

PURPOSE Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non–small-cell lung cancer who developed LMD and were subsequently treated with osimertinib. METHODS We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used. RESULTS Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months). CONCLUSION There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.

scholarly journals Brain Metastasis Mimicking Brain Abscess in ALK-Positive Non-Small-Cell Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Toshio Sakatani ◽  
Hidenori Kage ◽  
Shunsaku Takayanagi ◽  
Kaoru Watanabe ◽  
Yoshihisa Hiraishi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Brain Abscess ◽  
Cell Lung Cancer ◽  
Lung Resection ◽  
Brain Lesion ◽  
Small Cell ◽  
Small Cell Lung ◽  
The Brain

Brain metastasis frequently develops in non-small-cell lung cancer (NSCLC). Here, we report a patient who developed brain metastasis from ALK-positive NSCLC which mimicked brain abscess. He was admitted for suspected obstructive pneumonia nine months after curative lung resection. Head magnetic resonance imaging revealed a cavitary lesion, which was compatible with brain abscess but rare in brain metastasis. However, after treatment with antibiotics, the brain lesion increased in size. Aspiration of the liquid content of the brain lesion revealed cancer cells. When a brain lesion suggestive of abscess develops in a patient with ALK-positive NSCLC, aspiration may be necessary to differentiate metastasis from abscess.

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

Neurosurgery ◽  
2009 ◽  
Vol 64 (4) ◽  
pp. 664-676 ◽  
Author(s):  
Dima Suki ◽  
Mustafa Aziz Hatiboglu ◽  
Akash J. Patel ◽  
Jeffrey S. Weinberg ◽  
Morris D. Groves ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Stereotactic Radiosurgery ◽  
Tumor Resection ◽  
En Bloc Resection ◽  
Bloc Resection ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
En Bloc ◽  
University Of Texas ◽  
The Difference

Abstract OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSION 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.

Methylation profiling of EGFR mutant primary and metastatic lung cancer with brain metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20574-e20574
Author(s):  
Yasin Mamatjan ◽  
Michael Cabanero ◽  
Jessica Weiss ◽  
Jeffrey Zuccato ◽  
Hadas Sorotsky ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Lung Tumor ◽  
Molecular Subtype ◽  
Early Stage ◽  
Lung Tumors ◽  
Unsupervised Clustering ◽  
Egfr Mutant ◽  
Methylation Profiling

e20574 Background: EGFR-mutant lung cancer is a key molecular subtype of lung cancer. In recent years there is clear recognition in the value of using methylation signature of cancer for improving diagnosis and predicting outcome as well as understanding the biology of cancer progression. Methods: In this study we chose to characterize the methylome signature of early stage surgically resected EGFR-mutant lung adenocarcinomas in the primary lung tumor. 90 NSCLC cases and 7 matched metastatic brain samples were profiled using Illumina Infinium MethylationEPIC Beadchip. We compared methylation profiles of 1) smokers versus lifetime non-smokers and 2) matched primary lung versus brain metastasis to identify methylation biomarkers. We performed supervised analysis and unsupervised clustering of the methylation data. Results: Unsupervised clustering of all lung and brain samples based on 10K most variable probes showed a similar methylation signature between metastatic brain samples and lung samples. The 7-matched brain and lung samples formed close cluster groups based on matching pairs for the most variable probes from 2.5K to 10K, reflecting the same cell of origin. Supervised analysis of smokers versus lifetime non-smokers did not show any significant methylation differences between the two groups, while unsupervised analysis did not create clusters of smokers and non-smokers based on various number of probe sets we analyzed. Conclusions: Lung tumors that metastasized to the brain share similar methylation features with primary lung tumors. Comprehensive methylation profiling demonstrated no difference between EGFR mutant tumors in smokers versus non-smokers, suggesting that the EGFR mutation is a stronger determinant of outcome independent of smoking.

scholarly journals Management of Lung Cancer During the COVID-19 Pandemic

2020 ◽  
Vol 16 (9) ◽  
pp. 579-586 ◽  
Author(s):  
Aditi P. Singh ◽  
Abigail T. Berman ◽  
Melina E. Marmarelis ◽  
Andrew R. Haas ◽  
Steven J. Feigenberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Cancer Progression ◽  
Multidisciplinary Approach ◽  
Careful Consideration ◽  
Cancer Center ◽  
Risks And Benefits ◽  
Risk Of Mortality ◽  
The World ◽  
Life Threatening

Coronavirus disease 2019 (COVID-19) has had a devastating impact around the world. With high rates of transmission and no curative therapies or vaccine yet available, the current cornerstone of management focuses on prevention by social distancing. This includes decreased health care contact for patients. Patients with lung cancer are a particularly vulnerable population, where the risk of mortality from cancer must now be balanced by the potential risk of a life-threatening infection. In these unprecedented times, a collaborative and multidisciplinary approach is required to streamline but not compromise care. We have developed guidelines at our academic cancer center to standardize management of patients with lung cancer across our health care system and provide guidance to the larger oncology community. We recommend that general principles of lung cancer treatment continue to be followed in most cases where delays could result in rapid cancer progression. We recognize that our recommendations may change over time based on clinical resources and the evolving nature of the COVID-19 pandemic. In principle, however, treatment paradigms must continue to be individualized, with careful consideration of risks and benefits of continuing or altering lung cancer–directed therapy.

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