Almonertinib Combined with Anlotinib and Temozolomide in a Patient with Recurrent Glioblastoma with EGFR L858R Mutation.

Glioblastoma (GBM) is the most common primary brain tumor, and patients with GBM have a universally poor prognosis. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Interestingly, we identified an EGFR p.L858R mutation in a patient with recurrent GBM for the first time. Based on the genetic testing results, almonertinib combined with anlotinib and temozolomide was administered and obtained 12 months of progression-free survival after the diagnosis of recurrence as the fourth-line treatment. This is the first report that an EGFR p.L858R mutation was identified in a patient with recurrent GBM. Furthermore, this case report represents the first study applying the third-generation TKI inhibitor almonertinib in the treatment of recurrent GBM. The results of this study indicate that EGFR might be a new marker for the treatment of GBM with almonertinib.

Retrieval of sound-velocity profile in ocean by employing Brillouin scattering LiDAR.

Accurate remote sensing of the sound velocity profile of the upper-ocean mixed layers is of major important in oceanography, especially in underwater acoustic communication. However, the existing technologies cannot realize fast and real-time detection on sound velocity profile, a cost efficiency, flexibility, and real-time remote sensing technique is still highly urgent. In this paper, we propose a novel approach based on stimulated Brillouin scattering (SBS) LiDAR for retrieving the sound velocity profile. The sound velocity profiles in the upper-ocean mixed layer of South China Sea were retrieved theoretically and experimentally. We simulated the sound velocity profile of the upper-ocean mixed layer in South China Sea by using the Del Grosso algorithm and the data of temperature, salinity, depth selected from the World Ocean Atlas 2018 (WOA18). We designed a special ocean simulation system to measure the sound velocity in seawater with different temperatures, salinities, and pressures through measuring the frequency shift of SBS. Based on the measured sound velocities, we built a retrieval equation to express the sound velocity as a function of temperature, salinity, and pressure. Then, we retrieved the sound velocity profile of the upper-ocean mixed layer of South China Sea by using the retrieval equation. The results show that the retrieved sound velocity profile is good agreement with the theoretical simulation, and the difference between them is approximately 1∼2 m/s. Also, we have analyzed the differences between the theoretical simulation and experimental measurement. This work is essential to future application for remote sensing the sound velocity distribution profiles of the upper-ocean mixed layers by using the Brillouin LiDAR technique.

Rapid fabrication of sub-micron scale functional optical microstructures on the optical fiber end faces by DMD-based lithography.

The rapid development of optical fiber application systems puts forward higher requirements for the miniaturization and integration of optical fiber devices. One promising solution is to integrate diffractive optical microstructures on the end faces of optical fibers. However, rapid microfabrication on such tiny and irregular substrates is a challenge. In recent years, Femtosecond laser polymerization technology has become an effective solution to the challenge, which can be flexibly applied for the fabrication of complex 3D microstructures with ultra-high resolution. When the demand for the lithography resolution is not very high, other microfabrication methods with a lower technical threshold may be developed for achieving a balance between fabrication precision, cost and efficiency. In this paper, we report a Digital Micromirror Device (DMD) based lithography method dedicated to the fabrication of functional optical microstructures on the optical fiber end faces. Especially, it's also applicable to single-mode fibers (SMFs). By the projection via a 40x objective lens, the fabrication resolution of 0.405 µm was achieved within an exposure area of 209.92 µm × 157.44 µm. We evaluated the microfabrication results by the photomicrographs and the optical diffraction modulation effects of the functional optical microstructures. This method provides a new idea for fabricating both hybrid optical fiber devices and SMF devices, and it may be an alternative method for resolving the conflict between the precision, the cost and the efficiency.

Influence of temperature-salinity-depth structure of the upper-ocean on the frequency shift of Brillouin LiDAR.

Brillouin-based LiDAR is an alternative remote sensing technique for measuring the distribution profiles of temperature, salinity, and sound speed in the upper ocean mixed layer. Its principle is based on the dependence of Brillouin frequency shift on the temperature, salinity, and depth of ocean. Therefore, it is necessary to investigate the effect of various seawater parameters on Brillouin frequency shift for ocean remote sensing by using the Brillouin LiDAR. Here we theoretically and experimentally investigate the influence of temperature, salinity, and pressure (depth) of seawater on Brillouin frequency shift in the upper ocean for the first time. Numerical simulations of the distribution profiles of temperature, salinity, and Brillouin frequency shift in the upper-ocean mixed layers of East China Sea and South China Sea were performed, respectively, by employing the Brillouin equations and the World Ocean Atlas 2018 (WOA18). A special ocean simulation system was designed to carry out the stimulated Brillouin scattering (SBS) experiments for validating the numerical simulations. The results show that the seawater temperature is the most important factor for the Brillouin frequency shift in the upper-ocean mixed layer compared with the salinity and pressure. At the same salinity and pressure, the frequency shift increases by more than 10 MHz for every 1 °C increase in temperature. Also, the differences of Brillouin frequency shift between experimental and theoretical values at the same parameter conditions were analyzed. The experimental results coincide well with the theoretical simulations. This work is essential to future applications of Brillouin LiDAR in remote sensing of the temperature, salinity, or sound velocity profiles of ocean.

Successful treatment of an adult patient with diffuse midline glioma employing olaparib combined with bevacizumab.

Diffuse midline gliomas (DMGs), which are malignant, fast-growing and entail a poor prognosis, are a rare subtype of glial tumor. DMGs harboring H3 K27-mutation are a novel entity with a poorer prognosis than the H3 wildtype and are categorized as a grade IV glioma. Histone-mutated DMGs characterized by a midline location occur more commonly in children and less frequently in adults. Considering the DMG treatment is limited, there is an urgent need for effective therapeutic strategies. Olaparib is a poly-adenosine diphosphate-ribose polymerase inhibitor, which has been reported to inhibit glioma in preclinical and clinical trials. Olaparib plus bevacizumab has been successfully used in ovarian cancer. However, the application of olaparib in DMGs has not been reported yet. Herein, we firstly reported that an adult DMG patient benefited from olaparib combined with bevacizumab and achieved complete remission. The duration of response and overall survival was 8 months and 16 months respectively. This report provides a promising treatment option for patients with DMG.

Effects of temperature and pressure on the threshold value of SBS LIDAR in seawater.

Effects of temperature and pressure on the threshold value of stimulated Brillouin scattering (SBS) in seawater were analyzed theoretically and experimentally. Theoretically, the change of threshold value of SBS versus the ocean depth was simulated based on the International Thermodynamic Equation of Seawater-2010 (TEOS-10) and the World Ocean Atlas 2013 (WOA13). Experimentally, an ocean temperature and pressure simulator (OTPS) was designed to measure the threshold value of SBS through simulating the changes of temperature and pressure of seawater in 0∼1000 meters. The theoretical and experimental results exhibit that the threshold value of SBS decreases with the increase of temperature at the same seawater pressure and increases with the increase of pressure at the same seawater temperature. The results imply that the SBS process is more likely to occur in upper seawater of lower-latitude areas. The theoretical and experimental results are helpful for remote sensing in ocean using the SBS LIDAR.

Reduction of buried microstructure diffraction in fabricating curved microstructure by multiple exposure method.

When fabricating curved microstructure with DMD-based digital lithography, the buried microstructure formed in photoresist will introduce a distinct diffraction effect, which hinders the improvement in the fabrication fidelity. In this paper, a multiple exposure method is demonstrated to reduce the effect of buried microstructure diffraction. In this method, a high-space-frequency curved microstructure is decomposed into multiple low-space-frequency sub-microstructures, whose corresponding digital masks are successively exposed at the same position of substrate. Lithography experiments are implemented by introducing the multiple exposure method within the DMD-based digital lithography system. The experimental results show that the effect superimposed on the lithography pattern caused by the buried microstructure diffraction can be effectively reduced. In addition, we discuss the influence factors of buried microstructure diffraction by using FDTD method. The experimental results suggest that this fabrication method is potentially suitable for deep microstructure, particularly curved microstructure.

Clinical efficacy and biomarker analysis of neoadjuvant camrelizumab plus chemotherapy for early-stage triple-negative breast cancer: a experimental single-arm phase II clinical trial pilot study.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with a dismal prognosis. Immune checkpoint inhibitors have shown promising antitumor activity in neoadjuvant settings. This single-arm, phase II trial aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy as the neoadjuvant therapy (NAT) in early TNBC. METHODS: Patients received eight cycles of camrelizumab plus nonplatinum-based chemotherapy. The primary endpoint was total pathological complete response (pCR). Secondary endpoints included the breast pathological complete response (bpCR), adverse events (AEs). Multiomics biomarkers were assessed as exploratory objective. RESULTS: Twenty of 23 TNBC patients receiving NAT underwent surgery, with the total pCR rate of 65% (13/20) and bpCR rate of 70% (14/20). Grade ≥3 treatment-related AEs were observed in 14 (60.9%) patients, with the most common AE being neutropenia (65.2%). Tumor immune microenvironment was analyzed between pCR and non-pCR samples before and after the NAT. Gene expression profiling showed a higher immune infiltration in pCR patients than non-pCR patients in pre-NAT samples. Through establishment of a predictive model for the NAT efficacy, TAP1 and IRF4 were identified as the potential predictive biomarkers for response to the NAT. Gene set enrichment analysis revealed the glycolysis and hypoxia pathways were significantly activated in non-pCR patients before the NAT, and this hypoxia was aggravated after the NAT. CONCLUSION: Camrelizumab plus nonplatinum-based chemotherapy shows a promising pCR rate in early-stage TNBC, with an acceptable safety profile. TAP1 and IRF4 may serve as potential predictive biomarkers for response to the NAT. Aggravated hypoxia and activated glycolysis after the NAT may be associated with the treatment resistance.

The joint detection of CEA and ctDNA in cerebrospinal fluid: an auxiliary tool for the diagnosis of leptomeningeal metastases in cancer.

BACKGROUND: Leptomeningeal metastases (LMs) are highly invasive which leads to poor prognosis, but the accurate diagnosis of LM is challenging. It is necessary to investigate more advanced diagnostic methods to realize precision medicine. The main purpose of this study was to select a more effective method for the auxiliary diagnosis of LM by comparing various detection methods. The secondary purpose was to explore the value of cerebrospinal fluid (CSF) tumor markers (TMs) and circulating tumor DNA (ctDNA) testing in guiding clinical treatment. METHODS: TMs in serum and CSF of patients were detected by chemiluminescence. The ctDNA of CSF and plasma were detected by the next-generation sequencing (NGS) technology. RESULTS: In total, 54 tumor patients participated in this study, in which 39 with LM and 15 without LM (8 with parenchymal tumor and 7 without brain metastasis). The results showed that the sensitivity and accuracy of CSF cytology isolated during the first lumbar puncture were 0.31 (95% CI 0.17-0.48) and 0.50 (95% CI 0.36-0.64), respectively. The sensitivity and accuracy of CSF_CEA were 0.71 (95% CI 0.54-0.85) and 0.78 (95% CI 0.64-0.89), which were better than those of CSF_NSE and CSF_CFRA-211. The sensitivity and accuracy of CSF_ctDNA were 0.92 (95% CI 0.79-0.98) and 0.91 (95% CI 0.80-0.97), significantly higher than that of CSF cytology (P < 0.01). The sensitivity and accuracy of CSF_CEA combined with CSF_ctDNA were 0.97 (95% CI, 0.87-1.00) and 0.94 (95% CI 0.85-0.99), which were significantly higher than the traditional methods CSF cytology (P < 0.01). For LM patients with hydrocephalus, the sensitivity of CSF ctDNA even achieved 100% (14/14). CONCLUSION: CSF_CEA combined with CSF_ctDNA could be used to accurately distinguish patients with LM from those with no brain metastasis and from those with parenchymal tumors. CSF_ctDNA testing reveals a unique mutation profile for patients with LM. Dynamic detection of CSF TM and ctDNA can better predict the efficacy and reveal the cause of drug resistance to guide subsequent treatment. CLINICAL TRIAL REGISTRATION: Clinical trial registration number: NCT03029065.

Molecular genomic landscape of pediatric solid tumors in Chinese patients: implications for clinical significance.

PURPOSE: Pediatric solid tumors are significantly different from adult tumors. Studies have revealed genomic aberrations in pediatric solid tumors, but these analyses were based on Western populations. Currently, it is not known to what extent the existing genomic findings represent differences in ethnic backgrounds. EXPERIMENTAL: DESIGN: We retrospectively analyzed the basic clinical characteristics of the patients, including age, cancer type, and sex distribution, and further analyzed the somatic and germline mutations of cancer-related genes in a Chinese pediatric cohort. In addition, we investigated the clinical significance of genomic mutations on therapeutic, prognostic, diagnostic, and preventive actions. RESULTS: Our study enrolled 318 pediatric patients, including 234 patients with CNS tumors and 84 patients with non-CNS tumors. Somatic mutation analysis showed that there were significant differences in mutation types between CNS tumors and non-CNS tumors. P/LP germline variants were identified in 8.49% of patients. In total, 42.8% patients prompted diagnostic, 37.7% patients prompted prognostic, 58.2% patients prompted therapeutic, and 8.5% patients prompted tumor-predisposing and preventive, and we found that genomic findings might improve clinical management. CONCLUSIONS: Our study is the first large-scale study to analyze the landscape of genetic mutations in pediatric patients with solid tumors in China. Genomic findings in CNS and non-CNS solid pediatric tumors provide evidence for the clinical classification and individualized treatment of pediatric tumors, and they will facilitate improvement of clinical management. Data presented in this study should serve as a reference to guide the future design of clinical trials.

Age-dependent genomic characteristics and their impact on immunotherapy in lung adenocarcinoma.

BACKGROUND: The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD. METHODS: In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort. RESULTS: ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group. CONCLUSION: Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.

A Novel Germline SDHA Gene Mutation and Co-Occurring Somatic KIT Activating Mutation in a Patient With Pediatric Central Nervous System Germ Cell Tumor: Case Report.

Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of primary CNS tumors. GCTs are more common and mostly observed in pediatric and young adult patients. CNS GCTs are divided into germinomas and non-germinomatous germ cell tumors (NGGCTs), with different therapeutic strategies depending on diagnosis. Herein, we report a patient with pediatric central nervous system germinoma harboring a somatic KIT p.Y823D and a heterozygous germline SDHA p. T396Nfs*14 mutation detected by next generation sequencing. After surgery, the patient received chemotherapy (temozolomide + nedaplatin + etoposide). This is the first report of a Chinese pediatric patient with CNS GCT harboring concurrent germline SDHA and somatic KIT mutation, which enriches molecular profiles of CNS GCTs and provides more molecular evidence of clinical diagnosis and potential targeted therapy in CNS GCTs.

Effective treatment in lung adenocarcinoma patient with brain metastases harboring novel CLHC1/RNT4 intergenic region- ALK fusion: A case report.

RATIONALE: Anaplastic lymphoma kinase (ALK) fusion, an important oncogenic mutation, occurs in 3% to 7% of non-small cell lung cancer (NSCLC) cases, and EML4 is the most common partner gene. With the widespread application of next-generation sequencing (NGS), more gene breakpoint fusions have been discovered and functional fusion transcripts can provide targeted clinical benefits. PATIENT CONCERNS AND DIAGNOSIS: A 40-year-old woman was diagnosed with lung adenocarcinoma with brain metastases. A novel CLHC1/RNT4 intergenic region, ALK (Exon20-29) (abundance 39.97%), was identified using lung puncture tissue by NGS analysis (Simceredx), and results of immunohistochemistry and fluorescence in situ hybridization confirmed ALK fusion. INTERVENTIONS AND OUTCOMES: The patient was administered oral crizotinib (250 mg bid) combined with endostar (30 mg d1-7) for 12 cycles from June 18, 2020. The patient's condition was controlled, and the curative effect was evaluated as stable disease (SD). Unfortunately, brain magnetic resonance images showed multiple nodules in the left cerebellar hemisphere, and chest computed tomography showed no significant changes in the progression of the disease. Subsequently, alectinib (600 mg bid) was administered on April 1, 2021. Brain lesions were significantly reduced and partial remission (PR) was achieved. No significant changes were observed in the lung lesions. LESSONS: ALK fusion is a risk factor for brain metastasis (BM) in patients with advanced non-small NSCLC patients. In our case, a novel CLHC1/RNT4 intergenic region, ALK fusion, was identified for the first time in a lung adenocarcinoma patient with BM, who benefited from crizotinib and endostar sequential alectinib. Our case highlights the advantages of NGS for fusion detection and provides promising treatment options for NSCLC patients with BM harboring ALK fusions.

Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) improve outcomes for non-small-cell lung cancer (NSCLC) patients with ALK fusions. Nevertheless, ALK TKI resistance will inevitably occur. Histological transformation is one of the causes of TKI resistance in NSCLC. Reports of ALK-rearranged adenocarcinoma with histological transformation are limited. CASE PRESENTATION: A case of an invasive lung adenocarcinoma patient with ALK rearrangement who experienced histological transformation into sarcomatoid carcinoma after ALK TKI resistance is reported, and ALK fusion, MET amplification and TP53 mutation were detected after transformation. CONCLUSIONS: This case first reported a patient with invasive lung adenocarcinoma harboring ALK rearrangement who underwent histological transformation into sarcomatoid carcinoma after ALK TKI resistance, and MET amplification might represent the cause. After transformation, the patient benefited from targeted therapy combined with chemotherapy, which represents a promising option for patients with sarcomatoid carcinoma transformation.

Afatinib, an effective treatment for patient with lung squamous cell carcinoma harboring uncommon EGFR G719A and R776C co-mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) is a crucial driven gene in non-small cell lung cancer (NSCLC), and the EGFR mutation rate in lung squamous cell carcinoma (SCC) is only 3 ~ 6.92%. Uncommon EGFR mutations, such as S768I, L861Q and G719X, accounting for approximately 15% of NSCLC harboring EGFR mutation. Afatinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI), has been approved for NSCLC harboring uncommon mutations by the FDA in 2018. In our report, the lung SCC patient harboring uncommon compound EGFR mutation (G719A and R776C) benefited from afatinib. CASE PRESENTATION: A case of a lung SCC patient harboring uncommon compound EGFR mutation (G719A and R776C) benefited from afatinib, and new MYC amplification was detected by next-generation sequencing (NGS) after disease progression. CONCLUSIONS: This case first identified a patient with lung squamous cell carcinoma harboring uncommon compound EGFR mutation (G719A and R776C) benefited from afatinib and achieved 11 months of progression-free survival (PFS). Then, new MYC amplification was detected after disease progression, indicating that MYC amplification may be one of the reasons for afatinib resistance.

The First Case Report of a Patient With Oligodendroglioma Harboring CHEK2 Germline Mutation.

Introduction: CHEK2 (Checkpoint kinase 2) germline mutations were associated with an elevated risk of breast cancer, colorectal cancer, and other familiar cancers. Loss-of-function variants in CHEK2 are known to be pathogenic. Germline CHEK2 mutations have also been observed in medulloblastoma and primary glioblastomas. Currently, there is no direct evidence supporting the relationship of CHEK2 with central nervous system tumors. Case presentation: A case of an oligodendroglioma patient harboring the germline CHEK2 p.R137* mutation was reported. CHEK2 p.R137* mutation occurred in the forkhead-associated domain. Given the absence of other known genetic predisposing risk factors, we considered that oligodendroglioma might be associated with the CHEK2 mutation. The patient in our case might have a high risk of breast cancer and other multiple primary tumors. Her siblings and offspring would have a 50% chance of having the same variant. Conclusion: We reported a case of an oligodendroglioma patient with a family history of gastrointestinal tumors harboring the germline CHEK2 pathogenic variation. This is the first report of the association between the CHEK2 pathogenic variation and brain tumors that warrants further validation in larger cohorts.

Successful treatment of advanced pulmonary sarcomatoid carcinoma with the PD-1 inhibitor toripalimab: A case report.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung carcinoma (NSCLC), which characterized by insensitive to conventional radiotherapy and chemotherapy and poor prognosis. Except MET exon 14 alterations and other oncogene mutations, PSC commonly harbor high tumor mutational burden (TMB) and high level of PD-L1, which provide new therapeutic opportunities. Toripalimab (JS001) is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy. PD-1 combined with radiotherapy has been tried in several cancer types. CASE PRESENTATION: We reported a case of a PSC patient with PD-L1 overexpression responding to toripalimab and after progression the patients also benefits from toripalimab combined with local radiotherapy, which provides a promising option for PSC patients. CONCLUSION: This case provides the evidence of the effective role of toripalimab and PD-1 combined with local radiotherapy in PSC patients, which was the first application as far as we know.

A case report of a patient with first phenotype of papillary thyroid carcinoma and heterochronous multiprimary tumor harboring germline MUTYH Arg19*/Gly286Glu mutations.

MUTYH-associated polyposis (MAP) is an autosomal recessively inherited disease with multiple system tumors mainly in alimentary system. Tumor occurrence of MAP patients is highly heterogeneous in space and time. MAP is associated with germline biallelic mutations in MUTYH. The targeted next­generation sequencing technology and Sanger sequencing are the important methods to screen MUTYH mutations now. Herein, we identified a patient with heterochronous multiprimary tumor carring MUYTH Arg19*/Gly286Glu compound heterozygous mutations. The patient in this case had a first phenotype of thyroid cancer at age 44, which earlier 2 years than the alimentary system cancers. In conclusion, our case report creases the in-depth understanding of the MAP heterogeneous phenotype and further reminds recommendations for improvement of health management and genetic counseling, special treatment plans.

Erlotinib combined with bevacizumab and chemotherapy in first line osimertinib-resistant NSCLC patient with leptomeningeal metastasis: A case report.

RATIONALE: Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small cell lung cancer (NSCLC) with a poor prognosis. Osimertinib is a promising option for NSCLC with LM harboring epidermal growth factor receptor (EGFR) mutation. However, therapeutic approaches remain a challenge for osimertinib resistant NSCLCs with LM. Although studies have reported that the first/second-generation EGFR-tyrosine kinase inhibitors were active against osimertinib-resistant NSCLC with EGFR C797S and sensitive mutation (SM), the resistance inevitably occurred due to the development of the EGFR SM/C797S/T790M triple mutations. PATIENT CONCERNS: A 48-year-old woman was diagnosed with stage IV lung adenocarcinoma harboring the EGFR mutation in the combination of chest computed tomography, biopsy and amplification refractory mutation system-polymerase chain. One year and a half after oral administration of osimertinib, the patient progressed to extensive LM. DIAGNOSES: Magnetic resonance images of the brain showed extensive LM. Exfoliated tumor cells from cerebrospinal fluid (CSF) were positive detected by lumbar puncture and the cytology examination. EGFR mutations (exon19 E746_T751delinsI and exon20 C797S) in CSF circulating tumor DNA were detected by next-generation sequencing (NGS). INTERVENTIONS: Pemetrexed (800 mg day 1), cis-platinum (40 mg day 1-3) combined with bevacizumab (400 mg day 1) every 3 weeks were administered to the patient. After 1 cycle, due to optic nerve invasion, erlotinib was applied 150 mg/d combined with previous regimen. The patient continued erlotinib monotherapy after 6 cycles. OUTCOMES: After LM, erlotinib combined with pemetrexed, cis-platinum and bevacizumab were administered to the patient for 4.25 months based on the CSF NGS. Then, the patient continued erlotinib monotherapy and appeared disease progression after 10 months. The overall survival is 35 months. LESSONS: LM is a fatal complication of advanced NSCLC with a poor prognosis. NGS profiling of CSF circulating tumor DNA is important in NSCLC patients with LM and erotinib plus bevacizumab and chemotherapy is a promising option for patients with LM harboring EGFR C797S/SM.