bims-preonc 2025-02-16 papers

bims-preonc

Biomed News

on Precision oncology

Issue of 2025–02–16
thirteen papers selected by
Ankita Daiya, OneCell Diagnostics Inc.

Identification of circulating tumor DNA as a biomarker for diagnosis and response to therapies in cancer patients.
Circulating Tumor DNA and [18F]FDG-PET for Early Response Assessment in Patients with Advanced NSCLC.
Driver mutation detected in cerebrospinal fluid despite negative liquid biopsy results.
Circulating tumor DNA for surveillance in high-risk melanoma patients: a study protocol.
Case report: Clonal evolution analysis of a rare case of meningioma lung metastases identifies actionable alterations in matched longitudinal tumour samples.
CNS Outcomes of Osimertinib Plus Chemotherapy in Patients With EGFR Mutation Positive Lung Cancer Beyond Osimertinib Progression.
Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan.
Real-World Observational Study of Incidence and Outcomes in an HR+/HER2- Early Breast Cancer Population with High-Risk of Recurrence in Finland.
Can longitudinal biomarkers guide treatment decisions? Time will tell.
The Association Between Tumor Burden and the Efficacy of Immunotherapy Among Patients With Non-small Cell Lung Cancer.
Characterizing uveal melanoma patients with peritoneal metastases: A retrospective single-center analysis.
De Novo MET-amplified NSCLC treated with savolitinib achieved remarkable tumor regression: a case report and review of literature.
Case report: A case report and literature review on the efficacy of high-dose aumolertinib combined intrathecal pemetrexed by Ommaya reservoir for EGFR-mutated NSCLC with leptomeningeal metastasis as the initial symptoms.

Int Rev Cell Mol Biol. 2025 ;pii: S1937-6448(24)00123-0. [Epub ahead of print]391 43-93

Identification of circulating tumor DNA as a biomarker for diagnosis and response to therapies in cancer patients.

Ronan W Hsieh, Lynn K Symonds, Jason Siu, Stacey A Cohen.

  The sampling of circulating biomarkers provides an opportunity for non-invasive evaluation and monitoring of cancer activity. In modern day practice, this has typically been in the form of circulating tumor DNA (ctDNA) detected in plasma. The field of ctDNA has been a burgeoning technology, with prominent applications for blood-based cancer screening and in disease status assessment, especially after curative-intent surgery to evaluate for minimal residual disease (MRD). Clinical applications for the latter show an incredibly high sensitivity in certain cancer types with a need for additional studies to determine how much clinical decision-making should be adapted based on ctDNA results and which cancer types, stages, and treatments are best informed by ctDNA results. This chapter provides an overview of ctDNA detection as tool for cancer screening, detecting MRD, and/or molecularly characterizing a cancer, highlighting the rapidly amassing research as a prognostic biomarker and emerging data on ctDNA as a predictive biomarker.

Keywords:  Colorectal cancer; Liquid biopsy; Predictive; Prognostic; ctDNA

DOI:  https://doi.org/10.1016/bs.ircmb.2024.08.006
Diagnostics (Basel). 2025 Jan 22. pii: 247. [Epub ahead of print]15(3):

Circulating Tumor DNA and [18F]FDG-PET for Early Response Assessment in Patients with Advanced NSCLC.

Heidi Ryssel, Lise Barlebo Ahlborn, Danijela Dejanovic, Sune Hoegild Keller, Mette Pøhl, Olga Østrup, Annika Loft, Barbara Malene Fischer, Seppo Wang Langer, Andreas Kjaer, Tine Nøhr Christensen.

  Background/Objectives: Identifying treatment failure at earlier time points to could spare cancer patients from ineffective treatment and side effects. In this study, circulating tumor DNA (ctDNA) and [18F]FDG-PET/CT were investigated during the first cycle of anticancer therapy in patients with advanced non-small cell lung cancer (NSCLC) to explore their potential for early response evaluation. Methods: Patients with advanced NSCLC receiving first-line therapy with immune checkpoint inhibitors and/or chemotherapy were included. CtDNA and [18F]FDG-PET/CT assessments were conducted before treatment and at weeks 1 and 3 during the first cycle of therapy. ctDNA quantification was performed using a targeted next-generation sequencing (NGS) panel, and the least favorable change in any mutated allele frequency at a given time was used for analysis. [18F]FDG-PET/CT was quantified using sumSULpeak and metabolic tumor volume (MTV4.0). Early changes in ctDNA levels and [18F]FDG-PET parameters were compared with final treatment response, measured by RECIST after 12 weeks, as well as progression-free survival and overall survival. Results: Of the sixteen included patients, eight were non-responders. ctDNA mutations were detected in baseline blood samples in eight patients. Changes in ctDNA level, MTV4.0, and sumSULpeak at week 3 indicated response in 7 out of 8 patients, 13 out of 15 patients, and 9 out of 15 patients, respectively. At week 3, no false increases were seen with ctDNA and MTV4.0. Conclusions: These results suggest that early changes in ctDNA and [18F]FDG-PET/CT at 3 weeks of treatment could be used to early assess treatment response. Increased levels of ctDNA and MTV4.0 at week 3 were only observed in patients with treatment failure.

Keywords:  MTV 6; SUL 7; [18F]FDG-PET/CT 4; circulating tumor DNA 3; early response evaluation 5; keyword 1; non-small cell lung cancer 2; prognoses

DOI:  https://doi.org/10.3390/diagnostics15030247
Discov Oncol. 2025 Feb 10. 16(1): 145

Driver mutation detected in cerebrospinal fluid despite negative liquid biopsy results.

Kei Kunimasa, Daisuke Aohara, Kazumi Nishino.

  We report a case where a KRAS G12V driver mutation was identified in cerebrospinal fluid (CSF) but not in peripheral blood cell-free DNA (cfDNA) in a patient with advanced lung adenocarcinoma and significant central nervous system involvement. A 67-year-old man presented with hemoptysis and was diagnosed with stage IVB TTF-1-positive lung adenocarcinoma with brain and bone metastases. Standard chemotherapy was ineffective. While cfDNA analysis detected only a RAD21 mutation, CSF analysis revealed the KRAS G12V mutation. Despite the identification, no effective targeted therapy was available. This case highlights that CSF may be more suitable than peripheral blood cfDNA for detecting driver mutations in patients with predominant CNS lesions.

Keywords:  Cell free DNA; Cerebrospinal fluid; Driver mutation; Gene panel; Liquid biopsy

DOI:  https://doi.org/10.1007/s12672-025-01931-7
Acta Oncol. 2025 Feb 10. 64 229-233

Circulating tumor DNA for surveillance in high-risk melanoma patients: a study protocol.

Magnús P B Obinah, Sarah A Al-Halafi, Karin Dreisig, Tim S Poulsen, Christoffer Johansen, Thomas Litman, Stig E Bojesen, Estrid Høgdall, Annette H Chakera, Lisbet R Hölmich.

BACKGROUND AND PURPOSE: Melanoma is one of the deadliest skin cancers and challenges clinicians worldwide due to rising incidence, potential aggressiveness, and propensity for metastasis, necessitating comprehensive follow-up programs after primary treatment. Circulating tumor DNA (ctDNA) is a promising biomarker that may indicate disease progression earlier than traditional surveillance methods, including 18F-FDG PET-CT, ultrasound, and clinical examination. This study examines ctDNA detection in blood as a minimally invasive method for early identification of progression following primary treatment of melanoma. The aim is to overcome the limitations of current methods, potentially improving prognosis and survival.
PATIENTS/MATERIAL AND METHODS: Patients with high risk of recurrence following primary treatment of melanoma are offered inclusion. Blood sampling is performed at each follow-up visit. In case of recurrence, patient-specific mutations are identified through next-generation sequencing (NGS) of formalin and paraffin embedded tissue from diagnostic routine. Detection of mutation-specific ctDNA is performed on blood using digital droplet polymerase chain reaction (ddPCR) or NGS. This allows determination of the value and sensitivity of ctDNA for early detection of recurrence.
RESULTS AND INTERPRETATION: For validation purposes, we conducted a small pilot study using blood samples from 10 patients who had experienced recurrence and had a clinically confirmed BRAF V600E mutation. Detection of BRAF V600E ctDNA using ddPCR varied from 0/5 (0%) in DNA harvested from 4 mL plasma, to 3/5 (60%) in DNA from 8 mL of plasma. These results show promise and highlight the importance of high sensitivity and sampling volumes to ensure accurate detection of low levels of ctDNA.

DOI: https://doi.org/10.2340/1651-226X.2025.42515
Front Oncol. 2024 ;14 1483126

Case report: Clonal evolution analysis of a rare case of meningioma lung metastases identifies actionable alterations in matched longitudinal tumour samples.

Nicola Cosgrove, Orla M Fitzpatrick, Liam Grogan, Bryan T Hennessy, Simon J Furney, Sinead Toomey.

  Metastatic meningioma is rare, occurring in less than 1% of patients, and very few case studies have been reported, in particular for those that have spread to the lungs. Here we describe a rare case of metastatic meningioma to the lungs. Following a discussion at a medical oncology multi-disciplinary team meeting, whole genome sequencing was requested in November 2021 and discussed at a neurosurgical molecular tumor board in June 2022. Sequencing was performed on matched longitudinal collected samples of the primary tumor resection, the re-excised recurrent tumor after adjuvant radiation therapy, the lung metastases before treatment with sunitinib, and one paired blood sample for tumor-normal analysis. Whole genome characterization and clonal evolution analysis confirmed neurofibromatosis 2 (NF2) gene loss as the main driver of this cancer. In the same cancer clone as NF2, we identified a BRCA2 (p.E51K) mutation was present in all tumors, which may represent a potential driver event, though evidence supporting this is currently limited. Although this mutation is predicted to potentially influence homologous recombination, its clinical relevance as a biomarker for PARP inhibition remains speculative and requires further investigation. We also noted a SETD2 (p.S1885N) mutation that was present only in the recurrent tumor which was identified as a predicted biomarker of response to WEE1 inhibition. There was a stepwise increase in tumor mutational burden (TMB) from the primary meningioma to lung metastases, suggesting this patient may have been a candidate for immunotherapy.

Keywords:  driver mutations; lung metastases; meningioma; targeted therapies; whole genome sequencing

DOI:  https://doi.org/10.3389/fonc.2024.1483126
Clin Lung Cancer. 2025 Jan 11. pii: S1525-7304(25)00007-5. [Epub ahead of print]

CNS Outcomes of Osimertinib Plus Chemotherapy in Patients With EGFR Mutation Positive Lung Cancer Beyond Osimertinib Progression.

Wesley K Y Wong, Kevin K S Mok, Giselle P C Tsui, Olivia H Chen, Herbert H F Loong, Landon L Chan, Kelvin Yan, Frankie Mo, Kirsty W C Lee, K C Lam, Florence S T Mok, David Johnson, Allen C C Chen, Benjamin Lam, Matthew Lee, Tony S K Mok, Molly S C Li.

   BACKGROUND: Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC). Osimertinib in combination with chemotherapy beyond osimertinib progression may minimize CNS progression.
METHOD: In this retrospective analysis, patients with advanced EGFR mutation positive NSCLC and brain metastases who received platinum-based chemotherapy (PbChT) after disease progression on osimertinib were enrolled. The primary endpoint was real-world CNS progression-free survival (rwCNS-PFS) between patients who received PbChT with and without osimertinib continuation. Secondary endpoints included competing risk analysis of CNS progression and incidence of salvage radiotherapy to brain.
RESULTS: A total of 101 patients were analyzed, out of which, 39 (39%) continued osimertinib with chemotherapy (OSI+ cohort) and 62 (61%) received chemotherapy alone (OSI- cohort). Median rwCNS-PFS was significantly longer in the OSI+ cohort (9.0 months, 95% CI 6.6-11.4) than the OSI- cohort (5.7 months, 95% CI 4.6-6.9) (HR 0.37, 95% CI 0.18-0.76, P = .007). This remained significant after adjustment for EGFR mutation, line of osimertinib treatment, prior radiotherapy to brain, and CNS progression on osimertinib monotherapy. Estimated probability of CNS progression at 6 months was 5.6% in OSI+ cohort versus 20.9% in OSI- cohort. Incidence of salvage radiotherapy to brain was lower in the OSI+ cohort (15%) compared to OSI- cohort (24%).
CONCLUSION: In patients with EGFR mutation positive NSCLC and brain metastases, continuing osimertinib with chemotherapy after progression on osimertinib significantly reduced risk of CNS progression. Prospective studies are warranted to define the optimal treatment strategy for this patient population.

Keywords:  Brain metastase

DOI:  https://doi.org/10.1016/j.cllc.2025.01.007
Front Oncol. 2024 ;14 1484750

Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan.

Ünal Metin Tokat, Ashkan Adibi, Esranur Aydın, Şevval Nur Bilgiç, Eylül Özgü, Onur Tutar, Mutlu Demiray.

  Breast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone of first-line treatment in HR+/HER2+ BC is dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates of response and disease control in both HR+ and HR- cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete response in HR+ HER2-amplified and overexpressing metastatic BC twice through molecular tumor board (MTB) discussions: initially, with trastuzumab deruxtecan (T-DXd) when HER2 IHC was positive, and, then, with neratinib plus fulvestrant plus paclitaxel when IHC was negative. Our case presents GATA3 and NOTCH2 mutations, MCL1 and CKS1B amplifications, as well as ERBB3/KRAS overexpression and ER signaling as potential new mechanisms of resistance to T-DXd. Furthermore, we demonstrated that triplet combination could induce a remarkable response in the T-DXd-refractory setting, which could be explored in future clinical trials in HR+ and HER2-activated (by RNA or protein overexpression, amplification, and mutation) patients. Our case also highlights the importance of the MTBs to dynamically and reactively manage the course of disease and treatment on a per-patient basis.

Keywords:  HER2 antibody-drug conjugates (HER2 ADC); breast cancer; cancer genomics; molecular tumor board (MTB); neratinib; precision oncology; trastuzumab deruxtecan

DOI:  https://doi.org/10.3389/fonc.2024.1484750
Oncol Ther. 2025 Feb 14.

Real-World Observational Study of Incidence and Outcomes in an HR+/HER2- Early Breast Cancer Population with High-Risk of Recurrence in Finland.

Ravinder Singh, Samuli Tuominen, Mariann I Lassenius, Merja Auvinen, Astrid Torstensson, Tom Wiklund.

   INTRODUCTION: Real-world data on patients with early breast cancer (EBC) with high-risk features remains limited. This population-based study determined the incidence, outcomes and characteristics of patients with hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative EBC with high-risk features treated in everyday clinical care in two Finnish hospital districts which represent approximately 40% (2.5 million) of the total Finnish population (5.5 million).
METHODS: Adult female patients with BC (ICD-10 C50*) diagnosed between January 2012-June 2019 were indexed at the first BC diagnosis and followed until December 2019 or death. EBC was defined as having no records of metastasis within 90 days of index. High-risk status was defined as ≥ 4 positive axillary lymph nodes (ALNs) or 1-3 ALNs with either grade 3 tumor or tumor size ≥ 5 cm. Outcomes included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) and overall survival (OS) and were assessed using Kaplan-Meier methods and Cox regression models.
RESULTS: Among the 8678 patients with HR+/HER2- EBC, risk classification was feasible in 8081 (93.1%) individuals. Of these, 1407 (17.4%) were defined as high-risk and the remaining 6674 (82.6%) as low-risk patients. The average annual incidence of high-risk HR+/HER2- EBC in 2012-2018 was 21.8/100,000 women. Five-year invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) showed higher risk of recurrence for the high-risk group: IDFS 79.7% (95% CI 77.0-82.2) vs 89.3% (88.3-90.2) in the low-risk group; DRFS 82.4% (79.7-84.7) vs 92.9% (92.1-93.7) in the low-risk. Five-year overall survival (OS) in the high-risk group was 89.5% (87.3-91.4) and was 95.4% (94.7-96.0) in the low-risk group.
CONCLUSIONS: This study showed that high-risk patients account for 17% of newly diagnosed HR+/HER2- EBC in Finland. The high-risk profile was associated with increased risk of recurrence, distant relapse and death compared to low-risk patients. The poorer outcomes of high-risk HR+/HER2- EBC emphasizes a clear unmet need in improving the identification and treatment of these patients.

Keywords:  Distant relapse free-survival; Early breast cancer; HR+/HER2–; High risk of breast cancer recurrence; Incidence; Invasive disease-free survival; Outcomes; Overall survival; Patient characteristics; Real-world evidence

DOI:  https://doi.org/10.1007/s40487-024-00324-0
Clin Cancer Res. 2025 Feb 11.

Can longitudinal biomarkers guide treatment decisions? Time will tell.

Mark Y Jeng, Adam J Schoenfeld.

Defining patterns of acquired resistance has important prognostic and therapeutic implications in patients with lung cancer. Longitudinal biomarker analysis has enhanced our understanding of tumor biology and treatment response. However, the role of temporally informed biomarkers in guiding clinical decisions, such as local therapy intervention, remains unproven.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-4297
Cancer Control. 2025 Jan-Dec;32:32 10732748251320822

The Association Between Tumor Burden and the Efficacy of Immunotherapy Among Patients With Non-small Cell Lung Cancer.

Jia-Jun Hui, Han-Lu Yan, Sheng-Jun Ding, Bao-Dong Qin, Xiao-Dong Jiao, Yuan-Sheng Zang.

   BACKGROUND: This cohort study aimed to evaluate the impact of tumor burden (TB) on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS: Data from the POPLAR and OAK trials were extracted as the training and validation cohorts, respectively. TB was defined as the sum of the longest dimensions (blSLD) of measurable target lesions as per RECIST v1.1. The Kaplan-Meier curves and multivariate Cox regression analyses were performed to assess the association between TB with blood-tested tumor mutation burden (bTMB), PD-L1 expression, and survival outcomes. Additionally, random forest algorithms analysis was performed to evaluate the accuracy of TB in predicting 12-month mortality of NSCLC patients received atezolizumab.
RESULTS: A total of 105 patients from the POPLAR trial and 322 patients from the OAK trial were recruited in the training and validation sets, respectively. Patients with TB-L have significantly better OS than those with TB-H in the training (mOS: 15.8 months vs 6.93 months) as well as the validation (mOS: 16.0 months vs 7.59 months) cohort. The multivariate Cox regression analysis indicated that TB is an independent biomarker for OS prediction, regardless of bTMB, PD-L1 expression, and number of metastasis sites. The impact of TB on 12-month mortality was expected to be stronger with the increase of TB, suggesting that patients with a high tumor burden experienced a detrimental effect on 12-month mortality.
CONCLUSION: TB may act as a prognostic biomarker for clinical benefit in NSCLC patients treated with immunotherapy alone. This may be potentially effective for predicting the efficacy of immunotherapy-based regimens.

Keywords:  PD-L1 inhibitor; atezolizumab; biomarker; immunotherapy; non-small cell lung cancer; tumor burden

DOI:  https://doi.org/10.1177/10732748251320822
Eur J Cancer. 2025 Feb 06. pii: S0959-8049(25)00061-9. [Epub ahead of print]218 115280

Characterizing uveal melanoma patients with peritoneal metastases: A retrospective single-center analysis.

Stanislav Rosnev, Caroline A Peuker, Iris Piwonski, Jana Ihlow, Serge Leyvraz, Jonas Klingberg, David Horst, Maria Joosten, Markus Möbs, Antonia M Joussen, Maximilian de Bucourt, Ulrich Keilholz, Ulrich Keller, Sebastian Ochsenreither, Susanne M Rittig.

   BACKGROUND: Metastatic uveal melanoma (mUM) is an aggressive cancer predominately affecting the liver. Peritoneal metastases (PM) occur rarely, and there is limited knowledge about this subgroup´s clinical course and biology.
METHODS: We analyzed 41 mUM patients with confirmed PM from the Charité-Universitätsmedizin Berlin database, focusing on clinical characteristics, immune cell infiltrates, genetic alterations and tumor mutational burden (TMB).
RESULTS: The incidence of PM in mUM was 4.27 %. Metastatic disease was diagnosed 3.6 years after primary UM, with PM developing later (median: 4.7 years). Median overall survival (OS) from mUM diagnosis was 22.4 months. Prognosis correlated with metastatic pattern. Patients presenting with synchronous liver and peritoneal metastases or primary hepatic metastases followed by secondary peritoneal dissemination showed a median OS of 19.7 and 17.7 months, respectively. However, PM patients with exclusive extrahepatic disease at diagnosis of mUM had a significantly longer OS of 48.6 months and this metastatic pattern showed highly significant correlation with low and intermediate genetic risk. Metastasis-free survival and OS upon mUM diagnosis were significantly shorter in patients with high-risk UM tumors. TMB also correlated with metastatic pattern, being lowest in patients presenting with only extrahepatic disease. Higher TMB was generally associated with shorter OS.
CONCLUSION: PM in mUM patients is rare and in contrast to other extra-abdominal tumors does not worsen prognosis. Prognosis is greatly influenced by the metastatic pattern, which is determined by tumor biology, as evidenced by its correlation with genetic risk groups and TMB.

Keywords:  BAP1; Checkpoint inhibitors; Monosomy; Peritoneal metastases; Prognosis; Survival; Uveal melanoma

DOI:  https://doi.org/10.1016/j.ejca.2025.115280
J Cancer Res Clin Oncol. 2025 Feb 14. 151(2): 82

De Novo MET-amplified NSCLC treated with savolitinib achieved remarkable tumor regression: a case report and review of literature.

Jin Sheng, Juan Jiao, Na Yan, Hongming Pan.

  Primary MET amplification is an infrequent tumorigenic driver gene alteration identified in pulmonary neoplasms. Data on the effectiveness of MET-tyrosine kinase inhibitor (TKI) therapy in de novo MET amplification are relatively scarce, and there remains a dearth of empirical evidence supporting the use of precision therapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with primary MET amplification. We present a case of advanced lung adenocarcinoma in an elderly patient with primary MET amplification. The patient had an initial ECOG Performance Status (PS) 2. DNA-NGS analysis of tissue samples revealed a MET gene copy number (GCN) of 8, indicating MET amplification, without other oncogenic mutations associated with available drugs being detected. This finding was validated by MET fluorescence in situ hybridization (FISH), which showed cluster amplification. Initial treatment with savolitinib resulted in a sustained partial response lasting more than sixteen months. Our results suggest that savolitinib is effective and safe for the treatment of elderly patients with de novo amplified MET metastatic NSCLC and may therefore be considered a potential treatment option worthy of prospective study confirmation.

Keywords:  Case report; Non-small cell lung cancer; Primary MET amplification; Review; Senior patients; Targeted therapy

DOI:  https://doi.org/10.1007/s00432-025-06132-x
Front Oncol. 2025 ;15 1502934

Case report: A case report and literature review on the efficacy of high-dose aumolertinib combined intrathecal pemetrexed by Ommaya reservoir for EGFR-mutated NSCLC with leptomeningeal metastasis as the initial symptoms.

Maoxi Zhong, Li Zhou, Jing Guo, Chuan Chen, Wei Wang, Xiaoping Huang, Yi Liu.

  Leptomeningeal metastasis (LM) is a significant complication of advanced non-small cell lung cancer (NSCLC), occurring in only 3-5% of patients and exceedingly rare in newly diagnosed NSCLC patients. This also indicates that the tumor is highly malignant and aggressive, which brings great challenges to treatment. Here we present a case report of an EGFR-mutated NSCLC patient who presented with LM as the primary clinical manifestation, and review the latest advances in existing studies on LM-related treatment. The patient underwent multiple cycles of high-dose aumolertinib in combination with intrathecal pemetrexed administered via Ommaya reservoir. As of the submission date, the patient achieved significant remission and a LM Progression-Free Survival (PFS) exceeding 20 months. This case highlights the positive impact of high-dose aumolertinib combined with intrathecal pemetrexed on NSCLC patients presenting with severe meningeal symptoms as the initial manifestation, offering a viable therapeutic approach for managing severe meningeal symptoms associated with LM, such as headache, nausea, neck stiffness, and vomiting.

Keywords:  NSCLC; case report; high-dose aumolertinib; intrathecal chemotherapy; leptomeningeal metastasis

DOI:  https://doi.org/10.3389/fonc.2025.1502934