An open, multicenter, exploratory study of apatinib mesylate maintenance therapy for recurrent/metastatic head and neck squamous cell carcinoma (ChiCTR1800019375).

BACKGROUND: This study evaluated the efficacy of apatinib in maintenance therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). METHODS: Twenty-six patients from three centers were enrolled from November 2018 to September 2021. These patients received 2 weeks apatinib, administered at 250 mg qd. Then apatinib dose may be administered to 500 mg qd continuous in 4 weeks cycle if no patients experienced adverse reaction. Enrolled patients can receive a combination of radiotherapy or chemotherapy. The primary endpoints were progression-free survival (PFS), and secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), quality of life (QOL) score, and adverse drug reactions. RESULTS: Median PFS of all patients was 3.2 months (95% CI: 2.06-4.33). Median OS of all patients was 7.3 months (95% CI: 2.14-12.46). The DCR was 92.3%. The ORR was 30.8%. In univariate analysis, the results showed that ECOG score 0-1 (HR = 0.31, p = 0.006) and treated with apatinib for more than 60 days (HR = 0.31, p = 0.003) were independent prognostic indicators affecting PFS, and ECOG score 0-1 (HR = 0.40, p = 0.027) and moderately differentiated or highly differentiated (HR = 0.38, p = 0.048) were independent prognostic indicators of OS. The most common adverse events among treated subjects included hypertension (46.1%), fatigue (42.3%), and hand-foot syndrome (23.1%). There were only two cases (7.7%) of Grade III or above adverse reactions. CONCLUSIONS: Maintenance therapy with apatinib is an effective and well-tolerated regimen in patients with R/M HNSCC.

Postoperative therapy for local-advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Adjuvant therapy after surgery is effective for the treatment of advanced gastric cancer (GC), but the regimens are not uniform, resulting in imbalanced benefits. OBJECTIVES: To compare the overall survival (OS), relapse-free survival (RFS) and disease-free survival (DFS) of patients with local-advanced GC (LAGC) after surgery plus adjuvant therapy and with surgery alone based on meta-analysis. MATERIAL AND METHODS: Literature search was performed among the articles published in the PubMed, Embase and Cochrane Library databases from January 2000 to December 2018. Study selection was conducted based on the following criteria: randomized clinical trials (RCTs) on surgery plus adjuvant therapy compared to surgery alone; studies compared OS and/or RFS/DFS; and cases medically confirmed with LAGC. Only articles in English were included. RESULTS: A total of 12 datasets from 11 randomized controlled trials (RCTs) involving 4606 patients were included in the meta-analysis. There was a significant improvement in OS of patients who underwent postoperative adjuvant therapy (HR 0.78; 95% CI: 0.72-0.84; p < 0.001). In the subgroup analysis, it showed a higher improvement in OS patients who received adjuvant chemotherapy plus immunotherapy or radiotherapy (HR 0.72; 95% CI: 0.61-0.85; p < 0.001). CONCLUSION: Adjuvant therapy led to survival benefits in patients with LAGC.

Human-level play in the game of Diplomacy by combining language models with strategic reasoning.

Despite much progress in training artificial intelligence (AI) systems to imitate human language, building agents that use language to communicate intentionally with humans in interactive environments remains a major challenge. We introduce Cicero, the first AI agent to achieve human-level performance in Diplomacy, a strategy game involving both cooperation and competition that emphasizes natural language negotiation and tactical coordination between seven players. Cicero integrates a language model with planning and reinforcement learning algorithms by inferring players' beliefs and intentions from its conversations and generating dialogue in pursuit of its plans. Across 40 games of an anonymous online Diplomacy league, Cicero achieved more than double the average score of the human players and ranked in the top 10% of participants who played more than one game.

Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms.

Oxidative stress refers to the imbalance between oxidation and antioxidant activity in the body. Oxygen is reduced by electrons as part of normal metabolism leading to the formation of various reactive oxygen species (ROS). ROS are the main cause of oxidative stress and can be assessed through direct detection. Oxidative stress is a double-edged phenomenon in that it has protective mechanisms that help to destroy bacteria and pathogens, however, increased ROS accumulation can lead to host cell apoptosis and damage. Glioma is one of the most common malignant tumors of the central nervous system and is characterized by changes in the redox state. Therapeutic regimens still encounter multiple obstacles and challenges. Glioma occurrence is related to increased free radical levels and decreased antioxidant defense responses. Oxidative stress is particularly important in the pathogenesis of gliomas, indicating that antioxidant therapy may be a means of treating tumors. This review evaluates oxidative stress and its effects on gliomas, describes the potential targets and therapeutic drugs in detail, and clarifies the effects of radiotherapy and chemotherapy on oxidative stress. These data may provide a reference for the development of precise therapeutic regimes of gliomas based on oxidative stress.

Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome.

This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN's protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two C57/BL6 mice were randomly divided into control group (CON), SFN group, irradiation (IR) group, and IR plus SFN (IR/SFN) group. At eight weeks after irradiation, the morphological changes of mouse skin tissues were detected by H&E staining. Then, the oxidative stress and inflammatory response indexes in mouse skin tissues, as well as the expression of Nrf2 and its downstream antioxidant genes, were evaluated by ELISA, real-time PCR, and Western blotting. The H&E staining showed the hyperplasia of fibrous tissue in the mouse dermis and hypodermis of the IR group. Western blotting and ELISA results showed that the inflammasome of NLRP3, caspase-1, and IL-1ß, as well as oxidative stress damage indicators ROS, 4-HNE, and 3-NT, in the skin tissues of mice in the IR group were significantly higher than those in the control group (p < 0.05). However, the above pathological changes declined sharply after SFN treatment (p < 0.05). In addition, the expressions of Nrf2 and its regulated antioxidant enzymes, including CAT and HO-1, were higher in the skin tissues of SFN and IR/SFN groups, but lower in the control and IR groups (p < 0.05). SFN may be able to suppress the oxidative stress by upregulating the expression and function of Nrf2, and subsequently inhibiting the activation of NLRP3 inflammasome and DNA damage, so as to prevent and alleviate the RISI.

Progress and prospect in tumor treating fields treatment of glioblastoma.

Glioblastoma (GBM) is a challenging cancer with poor prognosis. The classical standard for treatment is safe resection, followed by concurrent chemoradiotherapy with subsequent adjuvant temozolomide (TMZ). Despite several attempts at different treatments, the 5-year survival rate remains poor. In recent years, with the continuous progress of treatment technology, tumor treating fields (TTFields) were preferable. The device could generate an intermediate frequency alternating electric field and induce apoptosis of some specific types of cancer cells with few toxic and side effects. TTFields induced apoptosis through multiple activations of the pathway. TTFields have been Food and Drug Administration (FDA)-approved for diagnosis and recurrent GBM as additional clinical trial results are revealed. This study reviewed the current status, mechanisms, correlations with immune pathways, the prospects of applying TTFields for GBM, and the adverse events.

Mesenchymal stromal cells can repair radiation-induced pulmonary fibrosis via a DKK-1-mediated Wnt/ß-catenin pathway.

Pulmonary injury occurring after thoracic radiotherapy is a main factor limiting the curative effect of radiotherapy. Robust activation of the Wnt signalling pathway induced by ionizing radiation stress plays a critical role in epithelial-mesenchymal transition (EMT) in irradiated type II alveolar epithelial cells and in the proliferation of pulmonary fibroblasts, which contributes to the formation of fibrotic lesions in irradiated lungs. The pathogenesis of radiation-induced pulmonary fibrosis could be restricted by systemic delivery of human adipose-derived mesenchymal stromal cells (Ad-MSCs), as evidenced by the inhibitory effects of Ad-MSCs on EMT in irradiated type II alveolar epithelial cells. The purpose of this study is to observe the effects of mesenchymal stromal cells (MSCs) on repairing fibrosis caused by radiation. We used western blotting and real-time PCR to observe the expression of DKK-1 in MSCs of different origins and passages. After the successful establishment of a radiation-induced lung injury model, we investigated the potency of the supernatant from stromal cells to reduce pro-fibrotic events, including EMT and fibroblast activation. To study the mechanism, we evaluated the levels of active ß-catenin, TCF4 and the target genes Snail, Twist and c-Myc. After the injection of Ad-MSCs into mice via the tail vein, proteins related to EMT, fibroblasts and Wnt/ß-catenin signalling were investigated. The TGF-ß and IL-10 protein concentrations in peripheral blood were measured by ELISA. Ad-MSC-derived supernatant effectively reversed the decrease in E-cadherin expression and inhibited the increase in vimentin expression induced by ionizing radiation in epithelial cells and suppressed the expression of α-SMA, a mediator of fibroblast proliferation. The canonical Wnt pathway may be activated by irradiation but the nuclear localization of active ß-catenin was reduced in the presence of the supernatant from Ad-MSCs. In addition, the expression of target genes involved in EMT was downregulated. Additionally, when DKK-1 in the supernatant was neutralized, all these effects were reversed. Changes in the levels of proteins related to EMT and fibroblast activation, as well as those of active ß-catenin and TCF4, were similar in vivo and in vitro. The serum level of the immunosuppressive factor IL-10 was increased after radiation and was further enhanced after Ad-MSC interference for one month. In conclusion, Ad-MSCs medium can contain DKK-1 and inhibit the induction of EMT via Wnt/ß-catenin signalling in vitro and in vivo.

Advances in radiotherapy and comprehensive treatment of high-grade glioma: immunotherapy and tumor-treating fields.

High-grade gliomas (HGGs) are the most common primary malignant brain tumors. They have a high degree of malignancy and show invasive growth. The personal treatment plan for HGG is based on the patient's age, performance status, and degree of tumor invasion. The basic treatment plan for HGG involves tumor resection, radiotherapy (RT) with concomitant temozolomide (TMZ), and adjuvant TMZ chemotherapy. The basic radiation technology includes conventional RT, three-dimensional conformal RT, intensity-modulated RT, and stereotactic RT. As our understanding of tumor pathogenesis has deepened, so-called comprehensive treatment schemes have attracted attention. These combine RT with chemotherapy, molecular targeted therapy, immunotherapy, or tumor-treating fields. These emerging treatments are expected to improve the prospects of patients with HGG. In the present article, we review the recent advances in RT and comprehensive treatment for patients with newly diagnosed and recurrent HGG.

Prevention and treatment of radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a common complication in cancer patients receiving local thoracic radiation and bone marrow transplantation conditioning. It is divided into early-stage radiation pneumonitis and advanced radiation fibrosis of the lung. This severely hampers the quality of life and survival of cancer patients. Meanwhile, RILI is a major factor limiting radiation doses in clinical practice, which affects the local control of cancer. Unfortunately, the mechanism of RILI is still not well defined, and there are no treatment options available for these patients. In this review we summarize the methods and agents used for the treatment and prevention of RILI, with the aim of increasing understanding of RILI.

Intestinal metastasis from breast invasive ductal carcinoma after a long latency: case report and literature review.

Intestinal metastasis from breast cancer (BC) is rarely encountered in clinical practice. Nonspecific symptoms and long latency result in misdiagnosis as a primary intestinal tumor. Therefore, increased awareness of bowel metastasis secondary to BC and a thorough understanding of the clinical and molecular features, and intervention of bowel metastasis are fundamental to avoid the delay of correct diagnosis and management. Herein, we documented a BC patient who experienced progressive bellyache and vomiting 16 years after simplified radical mastectomy. Abdominal CT scan revealed localized thickening of the small intestine wall and lumen narrowing, initially diagnosed as a primary intestinal tumor. The subsequent operation resolved the intestinal obstruction and confirmed the diagnosis of intestinal involvement of BC. Radical local treatment followed by systemic intervention contributed to a better outcome. Our case indicates that intestinal metastasis should be included in the diagnostic checklist in patients presented with any intestinal symptom even with a remote history of BC. Our case is of great value in its rarity and calls for the awareness of clinicians for this special entity to guarantee the accurate and prompt diagnosis and treatment, and optimize the patient's prognosis.

Leptomeningeal metastasis from solid tumors: clinical features and its diagnostic implication.

In this study, we examined the characteristics and aimed to increase the knowledge of clinical features of leptomeningeal metastasis (LM). The clinical data, including initial diagnosis and treatment of primary tumor, clinical manifestations, neuroimaging findings, cerebrospinal fluid (CSF) examination, were analyzed. For the patients with adenocarcinoma/breast cancer, the incidence of cranial lesions and cranial nerve paralysis was obviously higher than patients with small cell lung cancer. Whereas, the incidence of involvement of intravertebral canal was obviously lower than that of small cell lung cancer. Patients with adenocarcinoma/breast cancer showed more incidence of leptomeningeal enhancement compared to those with small cell lung cancer. Persistent severe headache was noticed in those with squamous carcinoma, and usually showed absence of abnormally LM-related neuroimaging and CSF cytological findings, which resulted in a challenge in the diagnosis of LM from squamous carcinoma. Patients with different primary tumors showed differential clinical features. Significant differences were observed in clinical features between patients with adenocarcinoma/breast cancer and small cell lung cancer. Our study contributes to the understanding of clinical characteristics of LM, and contributes to improvement of LM diagnosis in clinical practice.

Mesenchymal stem cells over-expressing cxcl12 enhance the radioresistance of the small intestine.

The chemokine C-X-C motif chemokine 12 (CXCL12) greatly impacts various biological processes in mammals, including cell survival, growth and migration. Mesenchymal stem cells (MSCs) are promising tools for carrying foreign genes to treat radiation-induced injuries in the intestinal epithelium. In this study, human adipose-derived MSCs were constructed to over-express the mouse cxcl12 gene to treat such injuries. In vitro, because of the high levels of mouse CXCL12 in conditioned medium produced by mouse cxcl12 gene-modified cells, phosphorylation of Akt at Ser473 and Erk1/2 at Thr202/Thr204 was increased within crypt cells of irradiated organoids compared with unmodified controls. Moreover, intracellular stabilization of ß-catenin was achieved after treatment of mouse cxcl12 gene-modified cells with conditioned medium. As a result, survival of crypt cells was maintained and their proliferation was promoted. When delivering mouse cxcl12 gene-modified cells into irradiated BALB/c nude mice, mice were rescued despite the clearance of cells from the host within 1 week. Irradiated mice that received mouse cxcl12 gene-modified MSCs exhibited reduced serum levels of interleukin-1α (IL-1α) and IL-6 as well as elevated levels of CXCL12. Additionally, epithelial recovery from radiation stress was accelerated compared with the irradiated-alone controls. Moreover, mouse cxcl12 gene-modified MSCs were superior to unmodified cells at strengthening host repair responses to radiation stress as well as presenting increased serum CXCL12 levels and decreased serum IL-1α levels. Furthermore, the number of crypt cells that were positive for phosphorylated Akt at Ser473 and phosphorylated Erk1/2 at Thr202/Thr204 increased following treatment with mouse cxcl12 gene-modified MSCs. Thus, cxcl12 gene-modified MSCs confer radioresistance to the intestinal epithelium.

Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single-arm study.

The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved-field radiotherapy (IF-RT) for treating LM from solid tumors with adverse prognostic factors. Fifty-nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1-3 times) was given before concurrent therapy. Thirty-eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20-70). Fifty-one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1-year-survival rate was 21.3%. Treatment-related adverse events mainly included acute meningitis, chronic-delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III-V toxic reactions. We concluded that IC combined with concomitant IF-RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective clinical study, the authors combined intrathecal methotrexate with involved-field radiotherapy in a concomitant regimen, showing that the approach can potentially improve quality of life for patients with adverse prognostic factors. Concurrent radiotherapy-bolstered IC by contributing to prolonged remission of neurological symptoms and increasing OS. The findings suggest that the concomitant regimen could be an optimal treatment option for LM.

Therapeutic effects of bone marrow-derived mesenchymal stem cells on radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a fatal condition featured by interstitial pneumonitis and fibrosis. Mesenchymal stem cells (MSCs) have been widely used for treating RILI in rodent models. In the present study, we aimed to investigate whether the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on RILI were in a dose-dependent manner. A total of 100 mice were randomly divided into: a control group (n=25), subject to lung irradiation and injection of phosphate-buffered solution (PBS) via the tail vein; and the hBM-MSC group, subject to lung irradiation followed by injection of a low dose (1x103 hBM-MSCs/g), medium dose (5x103 hBM-MSCs/g) and high dose (1x104 hBM-MSCs/g) of hBM-MSCs in PBS through the tail vein, respectively. After sacrifice, the pulmonary tissues were subject to hematoxylin and eosin (H&E) staining, Masson's trichrome staining and immunohistochemical staining to investigate the pathological changes. Immunofluorescent staining was performed to evaluate the differentiation capacity of hBM-MSCs in vivo by analyzing the expression of SPC and PECAM. hBM-MSCs improved the survival rate and histopathological features in the irradiated mice, especially in the low-dose group. Marked decrease in collagen deposition was noted in the irradiated mice treated using a low dose of hBM-MSCs. In addition, hBM-MSCs attenuated secretion and expression of IL-10 and increased the expression of TNF-α. Furthermore, hBM-MSCs had the potential to differentiate into functional cells upon lung injury. Low-dose hBM-MSCs contributed to functional recovery in mice with RILI.

ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive. The aim of our study is to systematically evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity. METHODS: Publications were identified through a search of the PubMed and Web of Science databases up to August 15, 2015. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between ERCC2 polymorphisms and radiotoxicity. Trial sequential analysis (TSA) and power calculation were performed to evaluate the type 1 and type 2 errors. RESULTS: Eleven studies involving 2584 patients were ultimately included in this meta-analysis. Conventional meta-analysis identified a significant association between ERCC2 rs13181 polymorphism and radiotoxicity (OR = 0.71, 95 % CI: 0.55-0.93, P = 0.01), but this association failed to get the confirmation of TSA. CONCLUSIONS: The minor allele of rs13181 polymorphism may confer a protect effect against radiotoxicity. To confirm this correlation at the level of OR = 0.71, an overall information size of approximate 2800 patients were needed.

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.

Thinprep plus Papanicolaou stain method is more sensitive than cytospin-coupled Wright Giems stain method in cerebrospinal fluid cytology for diagnosis of leptomeningeal metastasis from solid tumors.

BACKGROUND: The present study was designed to determine whether the Thinprep plus Papanicolaou stain (Thinprep) method is more sensitive than the Cytospin-coupled Wright-Giemsa (WG) stain (Cytospin) method in diagnosis of leptomeningeal metastasis (LM) from malignant solid tumors in cerebrospinal fluid (CSF). We also explored if the Thinprep method could be used in the differential diagnosis of the type of primary tumor cells based on the morphology of tumor cells in CSF samples. METHODS: The morphological features of tumor cells in fresh CSF samples were analyzed using both methods. The tumor cell detection rates were compared between the two methods. RESULTS: Using the Thinprep method, we found that each type of tumor cells in the CSF samples had specific identifiable morphological features linked to their primary cancer origins, such as adenocarcinomas originated from the lungs, breast, and stomach, and lung squamous cell carcinomas, small cell lung cancer, large-cell neuroendocrine lung cancer, hepatocellular carcinoma, and malignant melanoma. In a retrospective study with 88 LM patients, cancer cells were detected in 80 out of the 88 CSF samples. In the comparative study with 45 LM patients, the initial detection rate of the Thinprep method was significantly higher than that of the Cytospin method (73.3% vs. 57.8%, P<0.01). The cell morphology was better preserved and subcellular structures were clearer using the Thinprep method, compared to the Cytospin method. CONCLUSIONS: The Thinprep method is more sensitive and suitable for LM diagnosis in CSF in patients with malignant solid tumors than the Cytospin method. The Thinprep method may facilitate primary tumor detection and help design early treatment regimens for LM patients with tumors of unknown primary origin.

Leptomeningeal metastasis from early glottic laryngeal cancer: A case report.

The present study reports the case of a 53-year-old man with leptomeningeal metastasis from early glottic laryngeal cancer. The patient had been diagnosed with squamous cell carcinoma of the glottic larynx 9 years previously. The current symptoms included a recurring headache that had persisted for 1 month and vomiting for 1 week. A magnetic resonance imaging scan of the head revealed multiple enhancing lesions in the brain and multiple line-like enhancements in the brain fold. Computed tomography scans of the head, neck, chest and abdomen showed no nodular lesions. Cytological examination of the cerebral spinal fluid (CSF) revealed malignant cells with a scattered distribution pattern. The patient received intra-CSF methotrexate chemotherapy concurrent with whole-brain radiotherapy, which relieved the neurological symptoms. To the best of our knowledge, this is the first case of cytologically-confirmed LM from early glottic laryngeal cancer.