Clinicopathological, immunohistochemical and therapeutic approaches on survival in patients with epithelioid glioblastoma: Institutional experience in the management of 58 patients.

Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM.

Intrathecal anti-PD-1 treatment in metastatic melanoma patients with leptomeningeal disease (LMD): real-world data and evidence.

PURPOSE: Leptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD. METHODS: Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20 mg once every 2 weeks (n = 5) or pembrolizumab 20 mg once every 3 weeks (n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2-9). Efficacy and safety analyses were performed on all treated patients. RESULTS: From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1-45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1). CONCLUSIONS: In this real-world study, intrathecal anti-PD-1 treatment demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD.

TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases.

Background: The discovery of driver genes such as EGFR, KRAS, and ALK, has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear. Methods: Data from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers. Results: Among patients with NSCLC-BM, NGS revealed that TP53 was the most frequent mutation (61 %), with a detection rate of 39 %, closely by EGFR amplification. Additionally, CDKN2A, MYC, LRP1B, and RNF43 were frequently observed (18 %). The median OS was significantly shorter in the TP53 mutation group than in the wildtype group (14 versus undefined months, p = 0.014). Similar results were also found in the genetic alteration of EGFR amplification, suggesting that EGFR amplification was associated with worse OS (14 vs. 24 months, p = 0.039). Interestingly, NGS revealed that gene alternations such as TP53, EGFR amplification, and CDKN2A, tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including TP53 or EGFR amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples. Conclusions: Gene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

Intracranial management of HER-2 overexpression breast cancer with extensive volume or symptomatic brain metastases.

Objectives: This study aimed to evaluate the impact of high intracranial burden and symptomatic presentation of brain metastases on treatment outcomes in patients with HER-2 positive breast cancer. Through a retrospective analysis, we explored the intracranial responses following the application of HER-2 targeted therapy alone or in combination with other modalities and further elucidated the relationship between treatment efficacy, intracranial progression-free survival (PFS), overall survival (OS), and the burden of intracranial lesions and symptomatic presentations. Methods: A retrospective analysis was conducted on cases of HER-2 overexpressing breast cancer patients with brain metastases. Clinical records were reviewed to extract patient demographics, treatment modalities, and intracranial disease characteristics. Intracranial tumor burden was quantified at diagnosis and post-initial treatment. High intracranial tumor burden was defined as either total metastatic volume >15 cc, or the largest lesion >3 cm. Responses were assessed using established criteria. The correlation between intracranial disease parameters and intracranial progression-free survival (PFS) and overall survival (OS) was determined. Results: The study comprised 65 patients with HER-2 overexpression breast cancer and brain metastases. Symptomatic presentation was observed in 69.2% of patients at the diagnosis of brain metastases. Treatment with HER-2 target therapy alone or in combination with other modalities resulted in substantial intracranial responses, with 81.5% achieving at least a partial response at 3 months from therapy initiation. Median intracranial PFS and OS for patients with high intracranial burden were 9 and 22 months, respectively. Patients with high intracranial burden and symptomatic presentation at diagnosis demonstrated worse PFS and OS to those with lower burden and absence of symptoms (p < 0.05 for each). Conclusions: Her-2 overexpressing breast cancer and brain metastases face significant challenges, particularly those with high intracranial tumor burden, which correlates with poorer outcomes and higher incidence of leptomeningeal metastasis. Most patients responded positively to initial therapies, especially anti-HER-2 treatments combined with radiotherapy. Larger tumors necessitated more comprehensive treatment approaches, such as WBRT and SRS. Key factors influencing intracranial tumor control included the Ki-67 index, intracranial tumor burden, and continuous use of HER-2 targeted therapy post-diagnosis.

Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

OBJECTIVES: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. METHODS: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. RESULTS: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. CONCLUSION: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. CLINICAL RELEVANCE STATEMENT: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. KEY POINTS: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

Personalized therapy guided by longitudinal liquid biopsies for treatment of leptomeningeal disease from lung adenocarcinoma: A case report.

Molecular-based targeted therapies have significantly benefited certain patients with cancer; however, those with leptomeningeal disease (LMD) persistently exhibit a poor prognosis and are often excluded from clinical trials. Tumor-derived cell-free (cf)DNA, found in the cerebrospinal fluid (CSF) of patients with LMD, can assist in diagnosis and tracking of disease progression. However, the utilization of CSF to direct targeted cancer therapy has yet to be extensively explored. The present study reported the case of a patient with lung adenocarcinoma and LMD who was monitored by performing a series of liquid biopsies of CSF and blood. Targeted sequencing was performed on cfDNA from the CSF and plasma, and the variant allele frequencies (VAFs) of BRAF and NRAS mutations were assessed and analyzed in conjunction with the clinical presentation of the patient. The patient then underwent serial chemotherapy, radiation therapy, immunotherapy and targeted treatment based on the results of the liquid biopsies. Upon the LMD diagnosis, a BRAF p.V600E mutation was detected in plasma cfDNA. Consequently, the patient was treated with vemurafenib and responded favorably to this consolidation treatment for 13 months. After a relapse in July 2018, both BRAF p.V600E and NRAS p.Q61K mutations were detected in CSF supernatant and sediment cell samples, suggesting drug resistance. Therefore, the treatment strategy for the patient changed to cobimetnib plus vemurafenib. Notably, the changes of VAF in the CSF supernatant samples were associated with the clinical status of the patient. The patient survived for 33 months post-LMD diagnosis. The present case report highlights the potential use of liquid biopsy in personalized therapy, as it was instrumental in informing the combinational treatment plan of the patient, which ultimately proved beneficial.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

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.

Development and validation of a nomogram to predict leptomeningeal metastases in lung adenocarcinoma: Cervical lymph node metastasis is an important association factor.

BACKGROUND: The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs. METHODS: Two hundred and seventy-three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer-Lemeshow test were used for internal validation of the nomogram. RESULTS: Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912-0.979) for the training cohort and 0.861 (95% CI 0.761-0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes. CONCLUSIONS: We created a user-friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Furmonertinib and intrathecal pemetrexed chemotherapy rechallenges osimertinib-refractory leptomeningeal metastasis in a non-small cell lung cancer patient harboring EGFR20 R776S, C797S, and EGFR21 L858R compound EGFR mutations: a case report.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, due to the rarity of cases, the response of EGFR-TKIs in patients harboring uncommon compound EGFR mutations still needs to be determined. Here, we demonstrated the case of a 47-year-old smoker diagnosed with leptomeningeal metastasis from NSCLC and had EGFR20 R776S, C797S, and EGFR21 L858R compound mutations. He was treated with furmonertinib combined with intrathecal pemetrexed chemotherapy following progression on osimertinib, which led to clinical improvement and successfully prolonged his survival by 3 months. Regrettably, the patient eventually died from heart disease. This report provides the first reported evidence for the use of furmonertinib and intrathecal pemetrexed chemotherapy in NSCLC patients harboring EGFR R776S/C797S/L858R mutations who progressed on previous EGFR-TKIs.

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.

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.

Gene Signatures for Latent Radiation-Induced Lung Injury Post X-ray Exposure in Mouse.

Objective: To investigate the X-ray-specific sensitive genes and potential signaling pathways involved in the latent period of radiation-induced lung injury (RILI) in mouse models. Method: Mice were randomized into groups for whole thoracic irradiation with a single fraction of 20 Gy X-ray or 12.5 Gy carbon heavy ion. Lungs were harvested 3 weeks after the irradiation, whole RNA was extracted and detected with the genome-wide transcriptional microarrays. Differentially expressed genes (DEGs) were calculated for each group and the X-ray-specific sensitive genes were determined, followed by the gene enrichment analysis of those DEGs exploring the potentially relevant signaling pathways and biological processes in latent RILI. Results: Three weeks after irradiation, gene expression levels varied between groups. 76 up-regulated DEGs were determined with mice in the X-ray group and gene ontology enrichment analysis for biological process (GO-BP) obtained several processes which were associated with radiation reaction, mitotic, immune cell chemotaxis or metastasis, immune factors, p53 apoptosis, and tissue remodeling. KEGG signaling pathway enrichment analysis showed that those 76 up-regulated DEGs were enriched in p53, IL-17, FoXO, melanoma, and non-small-cell lung cancer signaling pathways. By comparing the DEGs in X-ray and heavy ion groups, X-ray-specific sensitive genes were determined, the top 10 genes were Adamts9, Aacs, Col6a2, Fdps, Mdk, Mcam, Stbd1, Lbh, Ak3, and Emid1. The expression level of the top 10 genes was found to be significantly higher in the X-ray group than in the control and heavy ion groups. Conclusion: Our research determined the X-ray-specific sensitive gene set in mice lungs after exposure to radiation. The gene set could be used as a genetic marker to suggest the latency of RILI. The enrichment analysis results suggested that the relevant signaling pathways were potentially involved in the development of RILI. Further validation of those genes and signaling pathways is needed to confirm these findings.

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.

Weak correlation between total psoas muscle area and sarcopenia index for children with brain tumor.

OBJECTIVE: The aim of this study is to determine whether the sarcopenia index (SI) is a viable measure of muscle mass in pediatric patients with brain tumors. METHODS: Retrospectively enrolled patients (1-16 years) who had serum creatinine (Cr) and cystatin C (CysC) levels evaluated within 28 days of an abdomen magnetic resonance imaging scan for the lumbar vertebrae 3-4 total psoas muscle area (tPMA) were studied. Variables were compared using their z scores calculated from age- and sex-dependent reference. We hypothesized that a low SI indicated less skeletal muscle, and therefore potentially indicated sarcopenia. RESULTS: The SI z score had no correlation with tPMA z score (r = 0.004). Both Cr and CysC levels were positively correlated with tPMA in z scores (r = 0.249 and 0.320). tPMA strongly correlated with body mass index in z scores (r = 0.582). The z scores of tPMA, Cr and CysC decreased with elevated World Health Organization grades of tumor, but the z scores of SI showed no significant dependence on WHO grades. CONCLUSION: The correlation of SI to muscle mass is very weak in our sample of pediatric patients with brain tumor. Its viability as biomarker for sarcopenia needs more study.