e14023 Background: Leptomeningeal metastasis (LM) from malignant melanoma remains a catastrophic event with a historical median survival of <3 months. While intrathecal (IT) administration of PD-1 antibodies has shown preliminary efficacy, the potential synergy between radiotherapy-induced immunogenic cell death and compartmentalized checkpoint blockade remains unexplored. We investigated the safety and survival impact of combining WBRT with IT PD-1 antibody therapy in this high-risk population. Methods: We retrospectively analyzed consecutive patients with melanoma LM treated with IT PD-1 antibodies at a single center between June 2022 and December 2024. The cohort was stratified by treatment modality: IT Monotherapy vs. Combination Therapy (WBRT delivered within 30 days of IT PD-1 initiation). The primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS), assessed by Kaplan-Meier analysis and Log-rank tests. Safety was rigorously graded per NCI-CTCAE v5.0, with specific focus on neurotoxicity and immune-related adverse events (irAEs). Results: A total of 20 patients were enrolled (Combination: n=13; Monotherapy: n=7). Baseline characteristics were well-balanced. The Combination arm achieved a striking survival advantage, with a median OS of 45.3 weeks (95% CI 28.7–NR) compared to 20.1 weeks (95% CI 13.3–NR) in the Monotherapy arm (HR 0.30 [95% CI, 0.04-0.68]; P = 0.021). Similarly, median iPFS was more than doubled in the Combination group (23.0 vs. 10.0 weeks; P < 0.001). The regimen was well-tolerated; there was no statistically significant difference in the incidence of Grade ≥2 adverse events between groups, and no unexpected severe neurotoxicity was observed. Conclusions: Concurrent WBRT and IT PD-1 blockade demonstrates potent synergistic activity in melanoma LM, delivering unprecedented survival outcomes (median OS >10 months) without amplifying toxicity. These findings suggest that radiotherapy may prime the CSF microenvironment for enhanced immune checkpoint efficacy. This novel multimodal strategy warrants validation in prospective randomized trials as a potential new standard of care.

The role of local cranial radiation (LCR) combined with third-generation tyrosine kinase inhibitors (TKIs) in the following the progression to leptomeningeal metastasis (LM) in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastasis (BM) remains unclear. This study investigates whether LCR combined with third-generation TKIs can influence the occurrence LM in EGFR-mutated NSCLC with BM. Patients diagnosed with EGFR exon 19del or exon 21 L858R mutant NSCLC with LM in Guangdong Sanjiu Brain Hospital were recruited into the study between January 1, 2018 and December 31, 2023. They were separated into two groups according to whether they received LCR during the period from BM to LM on not. The primary endpoints were the LM disease-free survival (LM-DFS) and LM rate. A total of 93 patients were enrolled, 60 in the TKIs group and 33 in the LCR + TKIs group. The median LM-DFS of the TKIs group and the LCR + TKIs group were 14.1 months (95

Background Leptomeningeal metastases (LM) in EGFR-mutated non–small-cell lung cancer (NSCLC) confer poor prognosis. The value of local multidisciplinary treatment (L-MDT) in the era of third-generation EGFR tyrosine kinase inhibitors (TKIs) remains uncertain. Methods We retrospectively analyzed patients with EGFR-mutated NSCLC and LM from the multicenter CLM-tree registry (NCT06718972) treated with third-generation TKIs plus ≥ 1 L-MDT modality, including intrathecal/intraventricular chemotherapy (iC), ventriculoperitoneal (VP) shunting, or radiotherapy. The primary endpoint was real-world overall survival (rwOS). Cerebrospinal fluid (CSF)–derived tumor cells were cultured using an optimized air–liquid interface system for ex vivo drug testing. Results Among 101 patients (median age, 56 years; 56% female), 81% received pemetrexed-based iC and 33% underwent VP shunting. Median rwOS was 12.0 months; 12- and 18-month survival rates were 49.5% and 33.2%. rwOS differed by LM timing (20.0 vs. 11.0 months; P = 0.004) and NCCN risk group (17.0 vs. 11.3 months; P < 0.001). In poor-risk patients, triple-modality L-MDT (VP shunt + iC + radiotherapy) improved rwOS versus other approaches (18.0 vs. 10.5 months; P = 0.011). Ommaya reservoir–based iC was associated with longer survival than lumbar puncture (13.0 vs. 9.5 months; P = 0.012). Neurological symptoms improved significantly after L-MDT. In one resistant case, CSF-derived cultures guided therapy and achieved remission. Conclusions Third-generation TKIs plus L-MDT, particularly intensified local strategies in poor-risk patients, prolonged survival and improved neurological outcomes in EGFR-mutated NSCLC with LM. CSF-derived tumor cultures may enable individualized treatment. Trial registration: Clinicaltrials (NCT06718972). Registered on Dec 2, 2024.

e14022 Background: Leptomeningeal metastasis (LM) from gastric cancer represents a terminal condition with poor prognosis, where the efficacy of systemic therapy is limited by the blood-brain barrier. While local strategies such as whole-brain radiotherapy (WBRT), intrathecal (IT) chemotherapy, and surgical decompression (e.g., VP shunt, EVD) are utilized, the clinical impact of combining these modalities remains under-investigated. We evaluated the real-world safety and survival outcomes of this multimodal strategy. Methods: We analyzed 15 patients with gastric cancer LM treated at Guangdong Sanjiu Brain Hospital. Treatment regimens integrated systemic therapy with distinct local therapeutic modalities and their combinations, including WBRT, IT chemotherapy, and neurosurgical interventions (Ommaya reservoir, VP shunt, or EVD). The primary endpoint was overall survival (OS) from the diagnosis of LM. Survival outcomes were assessed using Kaplan-Meier methods and Log-rank tests. Safety was graded according to CTCAE v5.0. Results: The median OS for the entire cohort was 6.9 weeks. The multimodal regimen demonstrated a favorable safety profile; no Grade 3-4 adverse events were recorded. Toxicities were predominantly Grade 1-2 hematologic. Device-related complications occurred in 13.3% of patients and were manageable. Analysis of specific modalities revealed significant survival benefits. The addition of WBRT conferred a highly significant survival extension compared to non-WBRT regimens (median OS: 7.7 vs. 3.5 weeks; Log-rank P = 0.0024). Similarly, patients receiving IT chemotherapy exhibited superior survival compared to the non-IT group (8.7 vs. 4.6 weeks; P = 0.045). The "Combined Local Therapy" cohort (comprising Surgery [VP shunt/EVD] + WBRT + IT) showed a strong trend toward improved survival compared to limited local therapy (9.9 vs. 5.4 weeks; P = 0.054). Furthermore, baseline CSF-CEA <5 ng/ml was identified as a robust predictor of prolonged survival (24.6 vs. 6.0 weeks; P = 0.0299). Conclusions: Comprehensive multimodal therapy is feasible and safe for patients with gastric cancer LM, showing zero severe toxicity. The significant survival benefit observed with WBRT and IT chemotherapy suggests that restoring CSF flow and reducing intracranial tumor burden are critical components of management. The combination of surgical intervention (VP shunt/EVD), WBRT, and IT chemotherapy offers a promising therapeutic strategy that warrants further validation.

BackgroundLeptomeningeal metastases (LM) from melanoma are rare and associated with dismal outcomes. Intrathecal PD-1 antibody therapy has shown encouraging activity in LM. Radiotherapy may enhance tumor immunogenicity and potentially augment immune checkpoint blockade within the central nervous system. The efficacy and safety of combining intrathecal PD-1 antibodies with whole-brain radiotherapy (WBRT) in melanoma LM remain unclear.MethodsWe retrospectively reviewed melanoma patients with LM who received intrathecal PD-1 antibody therapy between June 2022 and December 2024. Patients were categorized according to whether WBRT was administered within 30 days of intrathecal PD-1 antibody therapy: intrathecal monotherapy and combination therapy. Overall survival (OS) and intracranial progression-free survival (iPFS) were descriptively evaluated by treatment exposure, with between-group analyses considered exploratory and hypothesis-generating. Adverse events were graded using CTCAE v5.0.Results20 patients were included, of whom 7 received intrathecal PD-1 antibody monotherapy and 13 received intrathecal PD-1 antibody therapy combined with WBRT. The observed median OS was 20.1 weeks (95% CI, 13.3-not reached) in the intrathecal monotherapy group and 45.3 weeks (95% CI, 28.7-not reached) in the combination group. The observed median iPFS was 10.0 weeks (95% CI, 6.1-not reached) and 23.0 weeks (95% CI, 18.4-not reached), respectively. Treatment-related adverse events were manageable, and no new safety signals were identified.ConclusionIntrathecal PD-1 antibody therapy combined with WBRT showed numerically longer OS and iPFS than intrathecal therapy alone in this small retrospective descriptive series of melanoma leptomeningeal metastasis. These hypothesis-generating findings warrant prospective investigation but do not establish comparative efficacy.

e13017 Background: Up to 50% of patients with breast cancer (BC) and human epidermal growth factor receptor 2 (HER2) positive present with disease progression in brain metastases (BM). Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, has shown efficacy in active central nervous system(CNS) metastases. However, clinical efficacy of pyrotinib combining with stereotactic radiosurgery (SRS) in BCBM is unclear. Methods: This retrospective, observational study collected data from 52 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy in Guangdong Sanjiu brain hospital from 2019 to 2023. Among these patients, 36 received pyrotinib-based therapy combining with SRS concurrently, or within 1 months. Age, stage at diagnosis, dates of BM, primary tumor subtypes, prior systemic therapy, CNS-directed local therapy, the objective response and survival status were collected. The assessment of adverse effects was based on CTCAE 4.0. Results: 34 patients were evaluable for efficacy (median age: 51.5). With a median follow-up duration of 19.6 months, 1 patient (0.3%) achieved CR, while 27 patients (79.4%) had PR, resulting in an ORR of 82.3%. The median CNS PFS was 13.2 months (95% CI, 4.9-21.7). Median overall survival (OS) was 22.6 months (95% CI, 17.5-27.6). The most common grade 3 or worse treatment-emergent adverse event was diarrhea (6 [17.6%]). Conclusions: Our results suggest that pyrotinib combining with SRS is associated with promising efficacy and a satisfactory safety profile for Her2+ breast cancer brain metastases.

Up to 50% of patients with breast cancer (BC) and human epidermal growth factor receptor 2 (HER2) positive present with disease progression in brain metastases (BM). Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, has shown efficacy in active central nervous system(CNS) metastases. However, clinical efficacy of pyrotinib combining with stereotactic radiosurgery (SRS) in BCBM is unclear. This retrospective, observational study collected data from 52 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy in Guang dong Sanjiu brain hospital from 2019 to 2023. Among these patients, 36 received pyrotinib-based therapy combining with SRS concurrently, or within 1 months. Age, stage at diagnosis, dates of BM, primary tumor subtypes, prior systemic therapy, CNS-directed local therapy, the objective response and survival status were collected. The assessment of adverse effects was based on CTCAE 4.0. 34 patients were evaluable for efficacy (median age: 51.5). With a median follow-up duration of 19.6 months, 1 patient (0.3%) achieved CR, while 27 patients (79.4%) had PR, resulting in an ORR of 82.3%. The median CNS PFS was 13.2 months (95% CI, 4.9-21.7). Median overall survival (OS) was 22.6 months (95% CI, 17.5-27.6). The most common grade 3 or worse treatment-emergent adverse event was diarrhea (6 [17.6%]). Our results suggest that pyrotinib combining with SRS is associated with promising efficacy and a satisfactory safety profile for Her2+ breast cancer brain metastases.

OBJECTIVES:Intracranial non-germinomatous germ cell tumors (NGGCTs) are rare pediatric central nervous system (CNS) tumors. Growth impairment induced by radiation treatment was rarely evaluated. We aimed to evaluate the impacts of radiotherapy on height development as well as the dosimetric constraints, providing potential insights for hormonal replacement treatment. METHODS:A total of 128 pediatric patients diagnosed with NGGCTs were retrospectively studied. Sex, age at irradiation, physical doses and biologically effective dose (BED), height and endocrine status were obtained for analysis. The cumulative change in height was assessed using age-matched normalized height (ANH). Cumulative physical doses and BEDs for the whole brain and pituitary were derived via dose-volume histograms (DVHs) and BED-volume histograms (BEDVHs). RESULTS:For pediatric patients ≤ 11.5 years, linear correlations between ANH and cumulative physical doses as well as BEDs to the whole brain and pituitary were identified. More specifically, dosimetric constraints to the pituitary were 36 Gy for physical dose (AUC = 0.70 [95% CI, 0.54-0.86], p < .05) and 63 Gy2 BED (AUC = 0.69 [95% CI, 0.53-0.86], p < .05). Impaired hormone secretion with respect to growth hormone (GH) and thyroid-stimulating hormone (TSH) was observed following cranial irradiation (both p < .001), particularly for those with tumors at the suprasellar region (GH: p < .01, TSH: p < .001). Unlikely to patients > 11.5 years, the height development for patients with tumors in the suprasellar region was significantly more affected than those in the other locations (p < .01) among patients ≤11.5 years. CONCLUSIONS:Our study revealed the impacts of cumulative doses and tumor locations for radiation-associated growth impairment. Reduced levels of GH and TSH were observed in patients ≤ 11.5 years particularly with tumors in the suprasellar region.

Abstract Approximately 5% of patients with advanced non-small cell lung cancer may develop leptomeningeal metastasis (LM). 1,2 Patients with LM may have a poor prognosis; the median overall survival (OS) of LM NSCLC patients was only 3.6 to 11 months2,3. Although targeting therapies, particularly tyrosine-kinase inhibitors (TKI), are effective against primary tumors, the blood-brain barrier may limit their intracranial performance, resulting in variable patient survival outcomes. 4 LM patients have been shown to benefit from a variety of treatments, including surgery, radiation, systematic chemotherapy, targeted chemotherapy, immunotherapy, and intrathecal injection, but there is still a lack of conventional treatment paradigms for LM patients’ care. In patients with NSCLC, intrathecal administration, which delivers medications directly into the subarachnoid space via cerebrospinal fluid (CSF), was reported to be highly effective in controlling LM. 5,6 However, evaluating the efficacy of treatment for LM remains difficult and lacks standardization. Due to the diffusion of LM lesions, it is challenging to quantify tumor size using imaging techniques. Karnofsky performance score (KPS) is a commonly used assessment tool for functional impairment of LM 7, but it cannot disclose the tumor change in a quantifiable manner. Response Assessment in Neuro-Oncology (RANO) is a generally accepted response criterion that evaluates treatment response by incorporating a novel radiographic scorecard, CSF cytology or flow cytology, and neurological examination, while it was limited on measuring lesions for response assessment. 8,9 Recent research has demonstrated that circulating tumor DNA released by tumor apoptosis can be used as a biomarker to track treatment responses and tumor evolution. 10 Ct-DNA from cerebrospinal fluid (CSF) has also demonstrated superior intracranial response prediction performance compared to plasma. 11 In this study, patients with leptomeningeal metastasis (LM) who had undergone multiple courses of therapy received intrathecal pemetrexed (IP). Then, we monitored the dynamic changes in CSF-ctDNA to assess their response.

e21516 Background: LMD is one of the most severe complications of melanoma and has an extremely poor prognosis. Over the past decade, the incidence of LMD is increasing with improved treatment strategies and prolonged survival. This real-world study aims to evaluate the safety and efficacy of intrathecal anti-PD-1 treatment in MM patients with LMD. Methods: MM patients with LMD diagnosed by MRI and/or cerebrospinal fluid (CSF) cytology were assigned to intrathecal nivolumab infusion 20mg once every 2 weeks (n = 4) or pembrolizumab 20mg once every 3 weeks (n = 3). The patients received a median of 4 cycles of treatment (range 2–7 cycles). Efficacy and safety analyses were performed on all the treated patients. Results: Between June 2022 and December 2022, 7 patients were treated, including 3 cutaneous, 2 acral and 2 primary leptomeningeal melanoma. All patients presented linear or small nodular enhancement of leptomeningeal on MRI. Four patients had concurrent parenchymal brain metastases. The tumor cells were found in 5 patients by CSF cytology, and pathologic diagnosis was obtained by leptomeningeal biopsy in 2 patients. According to RANO-LM criteria, 4 patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while 3 patients developed progressive disease. The median overall survival (OS) was 39.7 months after initial diagnosis and 24 weeks after LMD. With a median follow-up of 13.3 weeks (range 9.4–20.3 weeks), the median intracranial progression-free survival (IPFS) and median OS for intrathecal anti-PD-1 were 16.1 and 20.3 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 was found to be well tolerated and effective in metastatic melanoma patients with LMD.

Intrathecal pemetrexed (IP) treatment represents a promising approach for managing leptomeningeal metastasis (LM) in cancer patients. However, a standardized and measurable method to evaluate the efficacy of IP for non-small cell lung cancer (NSCLC) patients with LM is currently lacking. This report describes three NSCLC-LM cases treated with IP following progression with tyrosine kinase inhibitors (TKIs) alone. We observed their responses through next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF). The outcomes were favorable for patient 1 and 2, whereas patient 3 experienced a relapse. Notably, changes in the allele frequency (AF) of ctDNA mutations corresponded with clinical outcomes across these patients, which were also corroborated by multiple traditional clinical markers. This observation is significant, particularly in patient 3, where ctDNA monitoring effectively described the patient's temporary improvement followed by deterioration. Furthermore, in patient 2, the transition from a positive to a negative cytological test, alongside persistent positive NGS results, underscores the higher sensitivity of NGS compared to conventional cytological analysis. This suggests that longitudinal ctDNA monitoring using CSF samples may serve as an effective and independent method for assessing and dynamically tracking the response to IP treatment in NSCLC-LM patients. This approach has the potential to refine therapeutic strategies and improve patient outcomes.

ObjectivesThis 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.MethodsA 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.ResultsThe 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).ConclusionsHer-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.

Abstract BACKGROUND HER-2 overexpression in breast cancer often leads to brain metastases, necessitating effective intracranial control strategies. This study aimed to evaluate the correlation between intracranial disease volume, symptomatic presentation, and treatment outcomes in HER-2 overexpressing breast cancer patients with brain metastases. 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). CONCLUSION Intracranial control in HER-2 overexpressing breast cancer patients with large volume or symptomatic brain metastases appears promising with combination with HER-2 targeted therapy and radiotherapy. Despite the varying intracranial disease burdens and symptomatic presentations, the use of HER-2 targeted therapy combined with radiotherapy demonstrates favorable intracranial responses, highlighting their potential in managing such cases.

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.

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.

Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis.

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.

Abstract OBJECTIVE To explore the basic situation of cognitive function in patients with initial state of brain metastasis and the potential factors affecting cognitive function, so as to find the critical value of cumulative tumor volume leading to cognitive dysfunction. METHODS A total of 284 patients who were newly diagnosed with brain metastases and underwent cognitive testing before radiotherapy in Guangdong Sanjiu Brain Hospital from 2016 to 2022 were retrospectively analyzed. The basic demographic information of the patients, KPS at the time of initial diagnosis, the number of brain metastases, the cumulative tumor volume, and the cognitive function test data before treatment were organized. RESULTS The cognitive impairment occurred in 100/284 patients (the criteria for cognitive impairment is that at least two of the eight sub-tests are less than 1.5 standard deviation or at least one is less than 2 standard deviations). Multivariate analysis showed that the number of tumors was not a factor in cognitive dysfunction. Age, gender, KPS, educational level, and cumulative tumor volume were risk factors affecting cognitive function. The cumulative tumor volume cut-off value for MOCA, HVLT-R immediate memory, HVLT-R delayed memory, VFT, TMT-A, and TMT-B cognitive impairment were 13.608, 13.125, 11.070, 14.523, 11.070, and 11.113 cc, respectively, while cut-off value for SDMT and TOL were 5.435 and 4.528 cc, respectively. CONCLUSIONS Before treatment, cognitive impairment of brain metastases had no significant correlation with the number of metastases but had a significant correlation with the cumulative tumor volume. The cumulative tumor volume cut-off value involving overall cognitive dysfunction, memory dysfunction, speech dysfunction, and decreased thinking speed is between 11-14.5 cc, and the cumulative tumor volume critical threshold involving executive dysfunction and computational dysfunction is between 4.5-5.5 cc.

ObjectiveTo 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.MethodsThe 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.ResultsIT 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.ConclusionPeri-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.

目的 探讨立体定向放射外科(SRS)治疗松果体区非生殖细胞瘤性生殖细胞肿瘤(NGGCTs)常规放疗后残留病灶的有效性和安全性.方法 回顾性分析 2008 年 1 月—2018 年 12 月广东三九脑科医院肿瘤中心收治的颅内生殖细胞肿瘤患者临床资料,按纳入标准筛选患者:(1)病理或临床诊断为NGGCTs;(2)病灶位于松果体区;(3)临床分期为局限期;(4)松果体病灶经过常规放疗50～54 Gy/25～30 f后可见肿瘤残留(病灶最大径直径＞10 mm).分析入组患者SRS治疗后肿瘤局部控制率、无进展生存时间、总生存时间及治疗相关毒性.结果 符合标准并纳入分析患者共27 例,均为男性患者,中位年龄16 岁(8～31 岁);随访至2019 年 12 月 30 日,2 例失访,中位随访时间 34 个月(8～142 个月);SRS治疗后 1 个月客观反应率71.4％,疾病控制率为 95.2％;3 年无进展生存时间、3 年总生存期分别为 85.2％、88％;单因素分析显示年龄、同步化疗与预后无关(P =0.286、0.824);放化疗前肿瘤部分切除术、AFP＞500 ng/mL、辅助化疗周期数≤4是不利预后因素(P =0.037、0.01、0.006);所有患者SRS治疗后未见急性放射反应,1 例(3.7％)出现远期治疗相关脑部神经毒性.结论 SRS治疗NGGCTs常规放疗后局部残留病灶安全、可行,耐受性好,可提高局部病灶控制,延长患者生存期,但由于病例数少需要进一步研究观察.