Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of non-small-cell lung cancer.

BACKGROUND: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM. METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing. RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044). CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.

PMS2 amplification contributes brain metastasis from lung cancer.

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

PD-1-induced encephalopathy: a report of 2 cases on neurological toxicities with immune checkpoint inhibitors.

Background: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis. Case Description: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy. Conclusions: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients' lives may be endangered. Thus, early identification and early treatment are very important.

Stroke as initial manifestation of non-small cell lung cancer with Trousseau syndrome.

OBJECTIVE: Stroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction. METHODS: The clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented. RESULTS: All 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038). CONCLUSION: Trousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.

Gastrointestinal signet ring cell malignancy: current advancement and future prospects.

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.

Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). METHODS: We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). RESULTS: A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. CONCLUSIONS: Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Mutational signatures of synchronous and metachronous brain metastases from lung adenocarcinoma.

Brain metastasis (BM) is an important cause of mortality for cancer patients. Many patients were diagnosed with brain metastases at their first visit who have not received any treatment while a subset of patients did not have distant metastases at the first visit and brain metastases were detected during the course of systemic therapies. The difference in their genomic characterization is unclear. 96 lung adenocarcinoma patients were enrolled in our study. 53 patients (55%) had synchronous metastatic brain tumors. 43 (45%) patients had metachronous brain metastases. We performed 168 panel-targeted gene sequencing cerebrospinal fluid (CSF) and plasma samples from patients to identify genomic features of synchronous brain metastases (SBM) and metachronous brain metastases (MBM). In conclusion, CSF liquid biopsies have a priority in detecting gene alteration. A comprehensive comparison of molecular profiling between SBM and MBM revealed the most frequently altered genes in both groups were EGFR and TP53, but with different exon point mutations. RTK-RAS and TP53 pathways were the most affected pathways.

Atypical primary central nervous system lymphoma and glioblastoma: multiparametric differentiation based on non-enhancing volume, apparent diffusion coefficient, and arterial spin labeling.

OBJECTIVES: To evaluate the multiparametric diagnostic performance with non-enhancing tumor volume, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) to differentiate between atypical primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). METHODS: One hundred and fifty-eight patients with pathologically confirmed typical PCNSL (n = 59), atypical PCNSL (hemorrhage, necrosis, or heterogeneous contrast enhancement, n = 29), and GBM (n = 70) were selected. Relative minimum ADC (rADCmin), mean (rADCmean), maximum (rADCmax), and rADCmax-min (rADCdif) were obtained by standardization of the contralateral white matter. Maximum cerebral blood flow (CBFmax) was obtained according to the ASL-CBF map. The regions of interests (ROIs) were manually delineated on the inner side of the tumor to further generate a 3D-ROI and obtain the non-enhancing tumor (nET) volume. The area under the curve (AUC) was used to evaluate the diagnostic performance. RESULTS: Atypical PCNSLs showed significantly lower rADCmax, rADCmean, and rADCdif than that of GBMs. GBMs showed significantly higher CBFmax and nET volume ratios than that of atypical PCNSLs. Combined three-variable models with rADCmean, CBFmax, and nET volume ratio were superior to one- and two-variable models. The AUC of the three-variable model was 0.96, and the sensitivity and specificity were 90% and 96.55%, respectively. CONCLUSION: The combined evaluation of rADCmean, CBFmax, and nET volume allowed for reliable differentiation between atypical PCNSL and GBM. KEY POINTS: • Atypical PCNSL is easily misdiagnosed as glioblastoma, which leads to unnecessary surgical resection. • The nET volume, ADC, and ASL-derived parameter (CBF) were lower for atypical PCNSL than that for glioblastoma. • The combination of multiple parameters performed well (AUC = 0.96) in the discrimination between atypical PCNSL and glioblastoma.

Efficacy and safety of combined immunotherapy and stereotactic radiosurgery in NSCLCBM patients and a novel prognostic nomogram: A real-world study.

Objective: To explore the effectiveness of combined immunotherapy (IT) and stereotactic radiosurgery (SRS) and address the gap between evidence-based clinical practice and academic knowledge of optimal timing of IT relative to SRS. In addition, to meet the unmet need for an up-to-date prognostic assessment model in the era of IT. Methods: The data of 86 non-small cell lung cancer brain metastasis (NSCLCBM) patients treated with SRS to 268 brain metastases (BMs) were retrospectively extracted from our hospital database. The Kaplan-Meier analysis was employed for overall survival (OS) and a log-rank test for comparison between groups. Cox proportional hazards regression models were used to identify the significant prognostic factors. The prognostic nomogram was established utilizing the rms package of R software. Results: IT was found to be associated with improved OS (from BM diagnosis: HR 0.363, 95% CI 0.199 - 0.661, P < 0.001; from SRS: HR 0.472, 95% CI 0.260 - 0.857, P = 0.014). Individuals who received IT in combination with SRS had better OS than those who didn't (from the day of BM diagnosis: 16.8 vs. 8.4 months, P = 0.006; from the day of SRS: 12 vs. 7 months, P = 0.037). Peri-SRS timing of IT administration was a significant prognostic factor for OS (from BM diagnosis: HR 0.132, 95% CI 0.034 - 0.517, P = 0.004; from SRS: HR 0.14, 95% CI 0.044 - 0.450, P = 0.001). Initiating IT after SRS led to superior OS than concurrent or before (from BM diagnosis: 26.5 vs. 14.1 vs. 7.1 months; from SRS: 21.4 vs. 9.9 vs. 4.1 months, respectively). Additionally, we build a nomogram incorporating IT, cumulative intracranial tumor volume (CITV), and recursive partitioning analysis (RPA), demonstrating a remarkable prognosis prediction performance for SRS-treated NSCLCBM patients. Conclusion: Peri-SRS IT is a promising approach in treating NSCLCBM, as improved OS was observed without significantly increasing adverse events. Receipt of IT post-SRS was associated with superior OS than those who received IT concurrently or before. Incorporating IT and CITV into the RPA index could augment its prognosis assessment value for SRS-treated NSCLCBM patients, predominantly in the wild-type.

EGFR amplification is a putative resistance mechanism for NSCLC-LM patients with TKI therapy and is associated with poor outcome.

Background: Leptomeningeal metastases (LM) have become increasingly common in non-small cell lung cancer (NSCLC) patients who harbor epidermal growth factor receptor (EGFR) mutation treated with EGFR-TKI and are correlated with inferior prognosis. Evidence in prior research demonstrated that EGFR amplification was more likely presented in advanced clinical stages and was associated with worse survival. However, whether EGFR amplification is a prognostic marker in NSCLC-LM is still inconclusive. Methods: This study enrolled patients diagnosed with NSCLC-LM from June 2019 to September 2021 and who had received previous EGFR-TKI at Guangdong Sanjiu Brain Hospital. Cerebrospinal fluid (CSF) samples were collected and subjected to targeted next-generation sequencing of 168 cancer-related genes. Clinical characteristics and overall survival (OS) were compared in patients with and without EGFR amplification. Results: This study enrolled 53 NSCLC-LM patients, all of whom had EGFR mutations. TP53 and EGFR amplifications are the two most frequent mutations in the study cohort, presenting at 72% (38 of 53) and 40% (21 of 53), respectively. The rate of EGFR amplification was much higher at the time of leptomeningeal progression than at initial diagnosis (p < 0.01). Karnoskfy performance status was poorer (p = 0.021), and CSF pressure was higher (p = 0.0067) in patients with EGFR amplification than those without. A multivariable Cox proportional hazard regression model showed that EGFR amplification was an independent prognostic factor for poorer OS (8.3 vs. 15 months; p = 0.017). The median OS was shorter in NSCLC-LM patients with mutated TP53 than those with wild-type TP53, but the difference was not statistically significant (10 vs. 17.3 months, p = 0.184). Conclusions: EGFR gene amplification could be a potential resistance mechanism to EGFR-TKI failure in NSCLC-LM and is associated with inferior clinical outcomes.

Gene alternation of cerebrospinal fluid in patients with leptomeningeal metastases of lung adenocarcinoma using next-generation sequencing.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a better prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the outcome of leptomeningeal metastasis (LM) remains poor. In addition, due to limited access to intracranial tumour tissue, gene alterations associated with leptomeningeal metastasis from lung adenocarcinoma (LM-LUAD) are unclear. METHODS: Forty-five patients with LM-LUAD from May 2019 to June 2021 in Guangdong Sanjiu Brain Hospital were enrolled in this study. Seventy-five percent (34/45) of patients with LM harbored EGFR mutations, and patients with progressive disease (PD) of LM had 3rd-generation EGFR-TKI therapy and were defined as Cohort 1; those without 3rd-generation EGFR-TKI therapy were defined as Cohort 2. Next-generation targeted panel sequencing (NGS) was performed in each cerebrospinal fluid (CSF) sample of the two cohorts, and 9/45 LM-LUAD patients had matched plasma (PLA). RESULTS: The common gene alterations discovered in the CSF of LM-LUAD were EGFR mutation (34/45, 75%), TP53 (25/45, 56%), CDKN2A (9/45, 20%), ALK (7/45, 16%), CTNNB1 (6/45, 13%), MET (5/45, 11%), APC (4/45, 9%), FGF4 (4/45, 9%), FGF3 (4/45, 9%), ERBB2 (4/45, 9%), and PIK3CG (4/45, 9%). Cooccurring mutations of TP53 and EGFR were found in 49% (22/45) of patients and correlated with poor prognosis. CDKN2A was identified in 20% (9/45) of patients and presented slightly shorter overall survival (OS) than those without (7.1 versus 8.8 months, p = 0.2). Cohort 1 had more genes associated with poor prognosis, consisting of CDK4, CDKN2A, PIK3CG, or PIK3CA, and YES1 and MET were more likely to be detected in cohort 2. The alteration of EGFR was comparable between CSF and matched PLA. Incidences of gene alterations such as CDK4, CDKN2A, MET, SOX2, JAK2, BRAF, and PIK3CG were more likely to be identified in CSF. All mutant allele frequencies (MAF) were much higher in CSF than in matched PLA. CONCLUSIONS: CSF could be a potential candidate for the genetic profiling of LM-LUAD, demonstrating the genetic characteristics of LM in EGFR-mutated lung adenocarcinoma on diverse EGFR-TKI therapies.

A Novel Six Autophagy-Related Genes Signature Associated With Outcomes and Immune Microenvironment in Lower-Grade Glioma.

Since autophagy and the immune microenvironment are deeply involved in the tumor development and progression of Lower-grade gliomas (LGG), our study aimed to construct an autophagy-related risk model for prognosis prediction and investigate the relationship between the immune microenvironment and risk signature in LGG. Therefore, we identified six autophagy-related genes (BAG1, PTK6, EEF2, PEA15, ITGA6, and MAP1LC3C) to build in the training cohort (n = 305 patients) and verify the prognostic model in the validation cohort (n = 128) and the whole cohort (n = 433), based on the data from The Cancer Genome Atlas (TCGA). The six-gene risk signature could divide LGG patients into high- and low-risk groups with distinct overall survival in multiple cohorts (all p < 0.001). The prognostic effect was assessed by area under the time-dependent ROC (t-ROC) analysis in the training, validation, and whole cohorts, in which the AUC value at the survival time of 5 years was 0.837, 0.755, and 0.803, respectively. Cox regression analysis demonstrated that the risk model was an independent risk predictor of OS (HR > 1, p < 0.05). A nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its robust predictive capacity. KM analysis revealed a significant difference in the subgroup analyses' survival. Functional enrichment analysis revealed that these autophagy-related signatures were mainly involved in the phagosome and immune-related pathways. Besides, we also found significant differences in immune cell infiltration and immunotherapy targets between risk groups. In conclusion, we built a powerful predictive signature and explored immune components (including immune cells and emerging immunotherapy targets) in LGG.

Case Report: Identification of a Novel GNAS Mutation and 1p/22q Co-Deletion in a Patient With Multiple Recurrent Meningiomas Sensitive to Sunitinib.

BACKGROUND: Although surgical resection can cure the majority of meningiomas, there are still approximately 20% of patients suffering from an aggressive course with recurrence or progression. In this study, we reported a novel GNAS mutation and 1p/22q co-deletion responding to sunitinib in a patient with multiple recurrent meningiomas. CASE PRESENTATION: A 53-year-old woman with meningioma was hospitalized due to postoperative tumor progression for 3 weeks. WHO grade I meningioma was pathologically diagnosed after the first three surgeries, but the second recurrence occurred approximately 3 years following the third surgery. Next-generation sequencing was performed on the first two recurrent samples. GNAS mutations and 1p/22q co-deletion were both identified, and amplification at 17q and chromosome 19 was also found in the second recurrent sample, based on which WHO grade II/III meningioma was diagnosed. The lesion in the left cerebellopontine angle area enlarged after use of radiotherapy combined with temozolomide chemotherapy for 2 months. When sunitinib was added, the residual lesions began to lessen and continuously reduced. CONCLUSION: This typical case suggested that timely molecular diagnosis for refractory meningiomas contributed to guiding the molecular classification and clinicians to make more reasonable individualized therapeutic regimens, consequently benefiting the patients. This case report also highlighted the potential role of sunitinib in the treatment of refractory meningiomas.

A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report.

Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, he developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript's submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patient with LM carrying EGFR G719S and L861Q.

Associations of indoor carbon dioxide concentrations, air temperature, and humidity with perceived air quality and sick building syndrome symptoms in Chinese homes.

The indoor environment influences occupants' health. From March 1, 2018, to February 28, 2019, we continuously monitored indoor temperature (T), relative humidity (RH), and CO2 concentration in bedrooms via an online system in 165 residences that covered all five climate zones of China. Meanwhile, we asked one specific occupant in each home to complete questionnaires about perceived air quality and sick building syndrome (SBS) symptoms at the end of each month. Higher CO2 concentration was significantly associated with a higher percentage of perceived stuffy odor and skin SBS symptoms. Higher relative humidity was associated with higher percentage of perceived moldy odor and humid air, while lower RH was associated with a higher percentage of perceived dry air. Occupants who lived in residences with high RH were less likely to have mucosal and skin SBS symptoms (adjusted odds ratio (AOR): 0.73-0.78). However, the benefit of high humidity for perceived dry air and skin dryness symptoms is weaker if there is a high CO2 concentration level.

Stereotactic radiosurgery for treatment of large cerebellum metastases from lung cancer.

BACKGROUND: Stereotactic radiosurgery (SRS) is an important treatment option. This report evaluated the efficacy and safety of SRS in patients with large cerebellum metastases from lung cancer. METHODS: Between September 2016 and January 2020, a total of 44 patients with large cerebellum metastases >2 cm from lung cancer were evaluated. A median dose of 20 Gy (range, 8-24 Gy) was delivered in 1 to 3 fractions for SRS treatment. The survival rate was analyzed with SPSS software 21.0 and compared by log-rank test using the Kaplan-Meier method. RESULTS: The median overall survival (OS) and neurological progression-free survival (PFS) were 10.5 months (range, 1-32 months) and 9.0 months (range, 1-32 months), respectively. The median diameter and volume of the metastases were 3.5 cm (range, 2.1-5.7 cm) and 12.5 cc (range, 1.8-39.7 cc), respectively. The median volume of peritumoral edema was 36.3 cc (range, 3.7-100.3 cc). The median ratio of tumor volume to cerebellum volume was 8.7% (range, 1.3-27.0%). The median ratio of peritumoral edema volume to cerebellum volume was 25.0% (range, 2.5-68.6%). Neurological symptoms were present in 97.7% (43/44) of patients. After SRS treatment, symptoms improved in 83.7% (36/44) patients, stabilized in 11.6% (5/44) patients, whilst two patients experienced symptomatic progression. Of the latter, one patient accepted emergency surgery and the other accepted palliative care. CONCLUSIONS: Large cerebellum metastases are amongst the most severe forms of brain tumors. Increased tumor volume and peritumoral edema volume correlate with the most severe symptoms. SRS may be an effective alternative treatment for large cerebellum metastases from lung cancer and may preserve neurological function.

Evaluation on efficacy and safety of the addition of X-knife therapy to gefitinib in NSCLC patients with symptomatic brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a widely used therapy for brain metastases(BMs) in Non-small cell lung cancer(NSCLC). However, its role in symptomatic patients with EGFR mutation remains unclear. We have retrospectively reviewed the clinical data of patients with symptomatic BMs whom received SRS as a salvage approach and concurrent gifitinib therapy. METHODS: Seven patients with primary NSCLC, symptomatic BMs, and EGFR mutation were identified in a retrospective review of patients treated with SRS using X-knife at Guangdong 999 Brain Hospital between 1 January 2012 and 31 August 2014. The median follow-up of these patients was 16 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain, and critical brain structures. Toxicities and complications were identified by clinical records. RESULTS: SRS(X-knife) was selected to be performed on seven patients (two males and five females) diagnosed with NSCLC and EGFR mutation due to the presence of encephaledema, compression of ventricles, or other complications. Neurological symptoms (such as paresis, aphasia, sensory and visual disturbances) were not present in any patients before or after SRS treatment, and the postoperative Karnofsky performance status(KPS) was improved in all patients. Median overall survival(OS) was 16 months and median progression free survival(PFS) was 10 months. CONCLUSIONS: The improvement of KPS and survival were reliable by SRS(X-knife) with concurrent gifitinib therapy in NSCLC patients with symptomatic BMs, and EGFR mutation. Given the small sample size, further prospective studies with a greater number of patients are warranted to confirm our results.

Bevacizumab rescue therapy extends the survival in patients with recurrent malignant glioma.

OBJECTIVE: We retrospectively studied the efficacy of bevacizumab as salvage therapy for recurrent malignant glioma with a focus on the overall survival (OS). METHODS: Patients who received a therapy other than surgery for recurrent malignant glioma were included. Efficacy was evaluated using MRI. Neurological function was evaluated using the Response Assessment in Neuro-Oncology (RANO). The survival rate was calculated using the Kaplan-Meier method. RESULTS: Fifty-one patients with recurrent glioma (31 grade III, 20 grade IV) were included. Among them, 22 subjects (43.1%) received bevacizumab. The median OS was 10.2 months (range, 1 to 27 months). Patients receiving bevacizumab had comparable OS (a median of 9.9 vs. 10.0 months) and similar 6-month survival rate (43% vs. 34%) to those who did not receive bevacizumab. A subgroup analysis failed to notice any significant difference in grade III glioma patients receiving bevacizumab vs. those who did not. The median survival was significantly longer at 8.9 months (range, 4 to 13 months) in grade IV glioma patients receiving bevacizumab than in those who did not (5.6 months, range, 2 to 7 months, P=0.042). The 6-month survival rate was higher (83%) in those who received bevacizumab than in those who did not (47%, P=0.046). No grade 3/4 adverse events were observed in any patient. CONCLUSIONS: Bevacizumab, as a rescue therapy, provides a survival benefit for recurrent grade IV glioma.