Background:Non-small cell lung cancer(NSCLC)patients with leptomeningeal metastasis(LM)have a very poor prognosis.Intrathecal pemetrexed(IP)has shown moderate efficacy in treating patients with NSCLC-LM.Myelosuppressi...Background:Non-small cell lung cancer(NSCLC)patients with leptomeningeal metastasis(LM)have a very poor prognosis.Intrathecal pemetrexed(IP)has shown moderate efficacy in treating patients with NSCLC-LM.Myelosuppression is the most common adverse effect following IP administration.Despite this trend,the specific risk factors contributing to IP-related myelosuppression remain unclear.Methods:This study conducted a retrospective analysis of lung adenocarcinoma(LUAD)patients with LM who received IP treatment at the Second Affiliated Hospital of Nanchang University from April 2017 to April 2024.Risk factors for myelosuppression were identified through univariate and multivariate logistic regression analyses.Non-linear relationships and determined the inflection points were subsequently determined using smooth curve fitting and threshold effect analysis.Results:A total of 95 patients were identified,among whom 64(68.42%)experienced myelosuppression,with 43(45.26%)cases classified as severe myelosuppression.Leukopenia emerged as the most prevalent form of myelosuppression.Age was established as an independent risk factor for both myelosuppression and its severe form.A nonlinear relationship between age and severe myelosuppression was observed.The risk of developing severe myelosuppression increased significantly with age,beyond the turning point of 58 years old(OR 1.28,95%CI 1.08–1.52;p 0.0042).Conclusions:Advanced age is=associated with the occurrence of myelosuppression and severe myelosuppression.The probability of developing severe myelosuppression increases significantly in individuals aged 58 years or older.展开更多
Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance me...Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.展开更多
AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four insti...AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration （3.6, 6.7 and 14.6 wk, P = 0.03, RR： 0.415, 95% CI：0.188-0.918）.CONCLUSION： Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.展开更多
Leptomeningeal metastasis is an uncommon but serious complication in patients with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5% of the patients, most commonly among patients with cancer...Leptomeningeal metastasis is an uncommon but serious complication in patients with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5% of the patients, most commonly among patients with cancers of breast and lung, melanoma, and gastrointestinal malignancies. Treatment goal is to improve survival and quality of the patients. Use of targeted therapies and immunotherapy has led to improved survival of patients with non-small cell lung cancer （NSCLC）. In this article, we review emerging data on use of mutation-specific agents and immunotherapy in the treatment of leptomeningeal metastasis among patients with NSCLC.展开更多
BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that ofte...BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.展开更多
BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have...BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have a poor prognosis.Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis.CASE SUMMARY A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital.She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance.epidermal growth factor receptor(EGFR)mutation was detected by genomic examination,so she was first treated with gefitinib for 10 months before acquiring resistance.Cell-free cerebrospinal fluid(CSF)circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation,while biopsy and cytology from the patient’s CSF and the first enhanced cranial magnetic resonance imaging(MRI)showed no positive findings.A month later,the enhanced MRI showed linear leptomeningeal enhancement,and the cytology and biochemical examination in CSF remained negative.Therefore,osimertinib(80 mg/d)was initiated as a second-line treatment,resulting in a good response within a month.CONCLUSION This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy.Moreover,the routine screening of chest CT with the novel coronavirus may provide unexpected benefits。展开更多
Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer,...Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer, expounding on its epidemiology, diagnostic standards, efficacy assessment, treatment advice, and other aspects.展开更多
BACKGROUND Prominent leptomeningeal contrast enhancement(LMCE)in the brain is observed in some pediatric patients during sedation for imaging.However,based on clinical history and cerebrospinal fluid analysis,the pati...BACKGROUND Prominent leptomeningeal contrast enhancement(LMCE)in the brain is observed in some pediatric patients during sedation for imaging.However,based on clinical history and cerebrospinal fluid analysis,the patients are not acutely ill and do not exhibit meningeal signs.Our study determined whether sevoflurane inhalation in pediatric patients led to this pattern of‘pseudo’LMCE(pLMCE)on 3 Tesla magnetic resonance imaging(MRI).AIM To highlight the significance of pLMCE in pediatric patients undergoing enhanced brain MRI under sedation to avoid misinterpretation in reports.METHODS A retrospective cross-sectional evaluation of pediatric patients between 0-8 years of age was conducted.The patients underwent enhanced brain MRI under inhaled sevoflurane.The LMCE grade was determined by two radiologists,and interobserver variability of the grade was calculated using Cohen’s kappa.The LMCE grade was correlated with duration of sedation,age and weight using the Spearman rho rank correlation.RESULTS A total of 63 patients were included.Fourteen(22.2%)cases showed mild LMCE,48(76.1%)cases showed moderate LMCE,and 1 case(1.6%)showed severe LMCE.We found substantial agreement between the two radiologists in detection of pLMCE on post-contrast T1 imaging(kappa value=0.61;P<0.001).Additionally,we found statistically significant inverse and moderate correlations between patient weight and age.There was no correlation between duration of sedation and pLMCE.CONCLUSION pLMCE is relatively common on post-contrast spin echo T1-weighted MRI of pediatric patients sedated by sevoflurane due to their fragile and immature vasculature.It should not be misinterpreted for meningeal pathology.Knowing pertinent clinical history of the child is an essential prerequisite to avoid radiological overcalling and the subsequent burden of additional investigations.展开更多
Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive brea...Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.展开更多
Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer.Its prognosis is ominous and therapy outcomes are disappointing.Herein,we present two p...Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer.Its prognosis is ominous and therapy outcomes are disappointing.Herein,we present two patients;one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer,who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment.Furthermore,a thorough and short review of the literature is carried out.展开更多
Objective:To report a rare case of otogenic tension pneumocephalus as a complication of a diffuse leptomeningeal glioneuronal tumor in a patient with a ventriculoperitoneal(V.P.)shunt.Patients:Twenty-three-year-old ma...Objective:To report a rare case of otogenic tension pneumocephalus as a complication of a diffuse leptomeningeal glioneuronal tumor in a patient with a ventriculoperitoneal(V.P.)shunt.Patients:Twenty-three-year-old man with a confirmed diffuse leptomeningeal glioneuronal tumor diagnosis was treated for temporal bone defect and considerable pneumocephalus one year after V.P.shunt.Intervention(s):The patient underwent a Transmastoid,retrolabyrinthine approach.The defect was closed with temporalis facia graft and conchal cartilage as a double-layer closure,and then DuraSeal®was placed over the repaired area.Main outcome measure(s):Resolution of the pneumocephalus.Results:There was a significant reduction in the pneumocephalus on the first day post-operatively.Conclusions:Spontaneous or secondary pneumocephalus development should be considered in patients with brain tumors,hydrocephalus,and patients who undergo V.P.shunt insertion.展开更多
BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non...BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.CASE SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.CONCLUSION This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.展开更多
Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metasta...Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.展开更多
Purpose: We present the case of a patient presenting with altered mental status on post-operative day seven after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed. Method...Purpose: We present the case of a patient presenting with altered mental status on post-operative day seven after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed. Methods: We discuss meningeal carcinomatosis in lung cancer, and describe challenges to diagnosis, therapy, and prognosis. Results: A review of the literature describing the clinical and oncologic principles of letomeningeal carcinomatosis in lung cancer is performed. Discussion: Leptomeningeal carcinomatosis (LC) occurs in approximately 5% of patients with non-small cell lung cancer and incurs a bleak prognosis. Presenting neurologic symptoms can be varied and diagnosis is confirmed via lumbar puncture and cerebrospinal fluid cytology. Few data exist regarding optimal treatment, although intrathecal chemotherapy has been shown to provide a modest improvement in median survival.展开更多
Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clari...Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clarify the pathophysiological changes of pLMCE.展开更多
Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with ...Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with no history of tumor whose first symptoms are headache and vision loss,and analyzed the causes why DLGNT is easy to be misdiagnosed as cryptococcal meningitis.Treatment remedies:the adolescent female presented with progressive exacerbations of headache,vomiting and vision loss after general treatment.Dynamic monitoring of routine biochemical changes in cerebrospinal fluid(CSF)found abnormal high CSF pressure and protein,repeated examination of antibodies and acid-fast bacilli were negative,and high-throughput pathogen gene examination excluded viral meningitis,tuberculous meningitis and other diseases.To save the optic nerve,the Ommaya capsule was implanted to reduce the intracranial pressure.After diagnostic antifungal treatment,the patient’s condition did not improve.To identify the etiology,extensive meningeal enhancement was eventually detected by enhanced magnetic resonance imaging(MRI),and highly atypical tumor cells were identified by repeated examination of fresh CSF cytology.Post treatment evaluating:for DLGNT,consult oncology.Meningeal biopsy and PET-CT(positron emission tomographycomputed tomography)examination were recommended,and intrathecal chemotherapy and whole-brain radiotherapy were performed according to the examination results.But the patient’s family refused to have a meningeal biopsy and asked to be released from the hospital.Conclusions:the adolescent female without a history of tumor can not rule out the disease,and cryptococcal meningitis also has meningeal enhancement.The gold standard for the diagnosis of DLGNT is to find cancer cells.There is no effective cure for DLGNT,the timely placement of Ommaya sac can significantly improve the quality of the patient’s life,and the active adoption of targeted therapy is expected to extend the patient’s survival.展开更多
Cerebral tuberculoma,a rare extrapulmonary tuberculosis manifestation,was reported in a 70-year-old man presenting with seizure-like episodes.MRI revealed a 13.6×45.1×7.9 mm left frontal extra-axial lesion w...Cerebral tuberculoma,a rare extrapulmonary tuberculosis manifestation,was reported in a 70-year-old man presenting with seizure-like episodes.MRI revealed a 13.6×45.1×7.9 mm left frontal extra-axial lesion with T1-isointense/T2-hyperintense signals,marked contrast enhancement,and adjacent leptomeningeal thickening.Negative thoracic/abdominal CT and inflammatory CSF findings initially suggested a neoplasm.Histopathological examination of the resected lesion confirmed granulomatous inflammation with acid-fast bacilli,thereby leading to the diagnosis.This case report emphasizes the importance of considering tuberculous granuloma in older patients with intracranial masses and inconclusive CSF studies.Multi-model imaging combined with biopsy remains critical for definitive diagnosis.Early surgical intervention and antitubercular therapy may improve outcomes.展开更多
Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in hu...Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.展开更多
Patients with leptomeningeal metastases(LM)from non-small cell lung cancer(NSCLC)have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy.In the past,some randomized clini...Patients with leptomeningeal metastases(LM)from non-small cell lung cancer(NSCLC)have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy.In the past,some randomized clinical trials have been conducted with heterogeneous inclusion criteria,diagnostic parameters,response evaluation and primary endpoints.Efforts to develop a standardized magnetic resonance imaging(MRI)assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid(CSF)are underway.This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC,in particular the role of MRI,CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease,as well as the most recent clinical trials on targeted therapies.Targeted therapy,such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors,represent a feasible treatment with encouraging results in terms of disease control and survival.For ineligible patients,immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance,although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.展开更多
基金funded by the National Natural Science Foundation of China(grant number 82360629,awarded to ZZM)the Jiangxi Provincial Health Department Project(grant number 202410026,awarded to ZZM,202510363,awarded to HYQ).
文摘Background:Non-small cell lung cancer(NSCLC)patients with leptomeningeal metastasis(LM)have a very poor prognosis.Intrathecal pemetrexed(IP)has shown moderate efficacy in treating patients with NSCLC-LM.Myelosuppression is the most common adverse effect following IP administration.Despite this trend,the specific risk factors contributing to IP-related myelosuppression remain unclear.Methods:This study conducted a retrospective analysis of lung adenocarcinoma(LUAD)patients with LM who received IP treatment at the Second Affiliated Hospital of Nanchang University from April 2017 to April 2024.Risk factors for myelosuppression were identified through univariate and multivariate logistic regression analyses.Non-linear relationships and determined the inflection points were subsequently determined using smooth curve fitting and threshold effect analysis.Results:A total of 95 patients were identified,among whom 64(68.42%)experienced myelosuppression,with 43(45.26%)cases classified as severe myelosuppression.Leukopenia emerged as the most prevalent form of myelosuppression.Age was established as an independent risk factor for both myelosuppression and its severe form.A nonlinear relationship between age and severe myelosuppression was observed.The risk of developing severe myelosuppression increased significantly with age,beyond the turning point of 58 years old(OR 1.28,95%CI 1.08–1.52;p 0.0042).Conclusions:Advanced age is=associated with the occurrence of myelosuppression and severe myelosuppression.The probability of developing severe myelosuppression increases significantly in individuals aged 58 years or older.
文摘Background:Leptomeningeal metastasis(LM)after third-generation EGFR-TKIs resistance carries a dismal prognosis.Limited blood-brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism.We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib.Method:A 53-year-old,never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer(NSCLC)developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg.Salvage therapy with zorifertinib(200 mg BID)plus firmonertinib(80 mg qd)was initiated.Results:Within 14 days,the coma resolved.Karnofsky Performance Status improved from 20 to 70.Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1.Only grade 1-2 diarrhea,rash,and transaminitis occurred and resolved with symptomatic care.Conclusion:The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure.Prospective validation is warranted.
基金Supported by The Dong-A University Research Fund and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST R13-2002-044-05001-0)
文摘AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration （3.6, 6.7 and 14.6 wk, P = 0.03, RR： 0.415, 95% CI：0.188-0.918）.CONCLUSION： Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.
文摘Leptomeningeal metastasis is an uncommon but serious complication in patients with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5% of the patients, most commonly among patients with cancers of breast and lung, melanoma, and gastrointestinal malignancies. Treatment goal is to improve survival and quality of the patients. Use of targeted therapies and immunotherapy has led to improved survival of patients with non-small cell lung cancer （NSCLC）. In this article, we review emerging data on use of mutation-specific agents and immunotherapy in the treatment of leptomeningeal metastasis among patients with NSCLC.
基金Supported by Special Research Project of Capital Health Development 2016,No.2020-2-2048.
文摘BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.
文摘BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have a poor prognosis.Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis.CASE SUMMARY A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital.She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance.epidermal growth factor receptor(EGFR)mutation was detected by genomic examination,so she was first treated with gefitinib for 10 months before acquiring resistance.Cell-free cerebrospinal fluid(CSF)circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation,while biopsy and cytology from the patient’s CSF and the first enhanced cranial magnetic resonance imaging(MRI)showed no positive findings.A month later,the enhanced MRI showed linear leptomeningeal enhancement,and the cytology and biochemical examination in CSF remained negative.Therefore,osimertinib(80 mg/d)was initiated as a second-line treatment,resulting in a good response within a month.CONCLUSION This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy.Moreover,the routine screening of chest CT with the novel coronavirus may provide unexpected benefits。
文摘Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer, expounding on its epidemiology, diagnostic standards, efficacy assessment, treatment advice, and other aspects.
基金This study was approved by the Ethics Committee of Aga Khan University Hospital on April 22,2020(2020-3611-9104).
文摘BACKGROUND Prominent leptomeningeal contrast enhancement(LMCE)in the brain is observed in some pediatric patients during sedation for imaging.However,based on clinical history and cerebrospinal fluid analysis,the patients are not acutely ill and do not exhibit meningeal signs.Our study determined whether sevoflurane inhalation in pediatric patients led to this pattern of‘pseudo’LMCE(pLMCE)on 3 Tesla magnetic resonance imaging(MRI).AIM To highlight the significance of pLMCE in pediatric patients undergoing enhanced brain MRI under sedation to avoid misinterpretation in reports.METHODS A retrospective cross-sectional evaluation of pediatric patients between 0-8 years of age was conducted.The patients underwent enhanced brain MRI under inhaled sevoflurane.The LMCE grade was determined by two radiologists,and interobserver variability of the grade was calculated using Cohen’s kappa.The LMCE grade was correlated with duration of sedation,age and weight using the Spearman rho rank correlation.RESULTS A total of 63 patients were included.Fourteen(22.2%)cases showed mild LMCE,48(76.1%)cases showed moderate LMCE,and 1 case(1.6%)showed severe LMCE.We found substantial agreement between the two radiologists in detection of pLMCE on post-contrast T1 imaging(kappa value=0.61;P<0.001).Additionally,we found statistically significant inverse and moderate correlations between patient weight and age.There was no correlation between duration of sedation and pLMCE.CONCLUSION pLMCE is relatively common on post-contrast spin echo T1-weighted MRI of pediatric patients sedated by sevoflurane due to their fragile and immature vasculature.It should not be misinterpreted for meningeal pathology.Knowing pertinent clinical history of the child is an essential prerequisite to avoid radiological overcalling and the subsequent burden of additional investigations.
文摘Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.
文摘Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer.Its prognosis is ominous and therapy outcomes are disappointing.Herein,we present two patients;one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer,who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment.Furthermore,a thorough and short review of the literature is carried out.
文摘Objective:To report a rare case of otogenic tension pneumocephalus as a complication of a diffuse leptomeningeal glioneuronal tumor in a patient with a ventriculoperitoneal(V.P.)shunt.Patients:Twenty-three-year-old man with a confirmed diffuse leptomeningeal glioneuronal tumor diagnosis was treated for temporal bone defect and considerable pneumocephalus one year after V.P.shunt.Intervention(s):The patient underwent a Transmastoid,retrolabyrinthine approach.The defect was closed with temporalis facia graft and conchal cartilage as a double-layer closure,and then DuraSeal®was placed over the repaired area.Main outcome measure(s):Resolution of the pneumocephalus.Results:There was a significant reduction in the pneumocephalus on the first day post-operatively.Conclusions:Spontaneous or secondary pneumocephalus development should be considered in patients with brain tumors,hydrocephalus,and patients who undergo V.P.shunt insertion.
基金Supported by the Medical and Health Science and Technology Planning Project,No.2019319609.
文摘BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.CASE SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.CONCLUSION This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.
基金Hainan Clinical Medical Center Construction Project(2021)Excellent Talent Team of Hainan Province(No.QRCBT202121)Key R&D Program of Hainan Province(No.ZDYF2022SHFZ109)。
文摘Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.
文摘Purpose: We present the case of a patient presenting with altered mental status on post-operative day seven after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed. Methods: We discuss meningeal carcinomatosis in lung cancer, and describe challenges to diagnosis, therapy, and prognosis. Results: A review of the literature describing the clinical and oncologic principles of letomeningeal carcinomatosis in lung cancer is performed. Discussion: Leptomeningeal carcinomatosis (LC) occurs in approximately 5% of patients with non-small cell lung cancer and incurs a bleak prognosis. Presenting neurologic symptoms can be varied and diagnosis is confirmed via lumbar puncture and cerebrospinal fluid cytology. Few data exist regarding optimal treatment, although intrathecal chemotherapy has been shown to provide a modest improvement in median survival.
基金Supported by the Chongging Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM013 and No.2023MSXM016.
文摘Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clarify the pathophysiological changes of pLMCE.
文摘Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with no history of tumor whose first symptoms are headache and vision loss,and analyzed the causes why DLGNT is easy to be misdiagnosed as cryptococcal meningitis.Treatment remedies:the adolescent female presented with progressive exacerbations of headache,vomiting and vision loss after general treatment.Dynamic monitoring of routine biochemical changes in cerebrospinal fluid(CSF)found abnormal high CSF pressure and protein,repeated examination of antibodies and acid-fast bacilli were negative,and high-throughput pathogen gene examination excluded viral meningitis,tuberculous meningitis and other diseases.To save the optic nerve,the Ommaya capsule was implanted to reduce the intracranial pressure.After diagnostic antifungal treatment,the patient’s condition did not improve.To identify the etiology,extensive meningeal enhancement was eventually detected by enhanced magnetic resonance imaging(MRI),and highly atypical tumor cells were identified by repeated examination of fresh CSF cytology.Post treatment evaluating:for DLGNT,consult oncology.Meningeal biopsy and PET-CT(positron emission tomographycomputed tomography)examination were recommended,and intrathecal chemotherapy and whole-brain radiotherapy were performed according to the examination results.But the patient’s family refused to have a meningeal biopsy and asked to be released from the hospital.Conclusions:the adolescent female without a history of tumor can not rule out the disease,and cryptococcal meningitis also has meningeal enhancement.The gold standard for the diagnosis of DLGNT is to find cancer cells.There is no effective cure for DLGNT,the timely placement of Ommaya sac can significantly improve the quality of the patient’s life,and the active adoption of targeted therapy is expected to extend the patient’s survival.
文摘Cerebral tuberculoma,a rare extrapulmonary tuberculosis manifestation,was reported in a 70-year-old man presenting with seizure-like episodes.MRI revealed a 13.6×45.1×7.9 mm left frontal extra-axial lesion with T1-isointense/T2-hyperintense signals,marked contrast enhancement,and adjacent leptomeningeal thickening.Negative thoracic/abdominal CT and inflammatory CSF findings initially suggested a neoplasm.Histopathological examination of the resected lesion confirmed granulomatous inflammation with acid-fast bacilli,thereby leading to the diagnosis.This case report emphasizes the importance of considering tuberculous granuloma in older patients with intracranial masses and inconclusive CSF studies.Multi-model imaging combined with biopsy remains critical for definitive diagnosis.Early surgical intervention and antitubercular therapy may improve outcomes.
文摘Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.
文摘Patients with leptomeningeal metastases(LM)from non-small cell lung cancer(NSCLC)have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy.In the past,some randomized clinical trials have been conducted with heterogeneous inclusion criteria,diagnostic parameters,response evaluation and primary endpoints.Efforts to develop a standardized magnetic resonance imaging(MRI)assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid(CSF)are underway.This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC,in particular the role of MRI,CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease,as well as the most recent clinical trials on targeted therapies.Targeted therapy,such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors,represent a feasible treatment with encouraging results in terms of disease control and survival.For ineligible patients,immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance,although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.
