Reported PFS values were: replacement EGFR-TKI (1.9-4.4 months), platinum-pemetrexed chemotherapy (1.6-20.7 months), osimertinib plus platinum-pemetrexed (3.9-6.9 months), chemotherapy plus anti-angiogenic agents (1.8-16.8 months), and chemotherapy plus immune checkpoint inhibitors (3.8 months). Post-progression molecular testing and, where feasible, tissue re-biopsy are important to guide subsequent treatment decisions. Second-line outcomes were variable, with chemotherapy combined with anti-angiogenic agents showing numerically longer progression-free survival in a small subgroup; however, these findings are descriptive due to the small sample size and treatment heterogeneity.

Clinical courses were heterogeneous: one patient achieved a durable partial response using combined osimertinib and crizotinib. A second patient, intolerant to dual TKI therapy due to QTc prolongation and grade 3 edemas, achieved a sustained partial response with platinum-pemetrexed chemotherapy...However, its biological significance, driver versus passenger role, and therapeutic relevance remain uncertain. Combined EGFR and ROS1 inhibition may be considered in selected cases, but further validation is required.

Serial CSF sampling also captured treatment-associated molecular shifts, including progressive TYMS amplification during intrathecal pemetrexed in an exploratory case. Together, these findings support low-input CSF sequencing as a practical molecular approach to complement LM diagnosis and longitudinal monitoring in lung cancer and provide a rationale for prospective validation in independent multi-center cohorts.

Stereotactic brain biopsy confirmed PCNSL, and the patient was initiated on high-dose methotrexate-based chemotherapy with adjunctive dexamethasone. This case highlights that PCNSL can occur despite immunologic preservation in HIV and may present acutely with seizures. Early contrast-enhanced MRI, careful timing of corticosteroid use relative to biopsy, and timely referral are essential, particularly in resource-limited settings.

This study estimated the cost-effectiveness of sacituzumab tirumotecan (Sac-TMT) versus pemetrexed-platinum chemotherapy as second-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in China. A price reduction exceeding 73.81% would bring the ICER below the WTP threshold. At current prices, Sac-TMT is not cost-effective as second-line therapy for advanced EGFR-mutated NSCLC in China.

To evaluate the intracranial delivery of BTK inhibitor(BTKi), patient-derived PCNS-LBCL xenografted mice models were treated with highly-selective BTKi orelabrutinib, either monotherapeutically or in combining with methotrexate...The mutations in CSF circulating tumor DNA (ctDNA) rather than plasma-ctDNA were more consistent to those in tumor tissue, indicating that CSF-ctDNA is a useful tool for monitoring PCNS-LBCL. In summary, our data provided the molecular rationale as well as clinical evidences that incorporation of BTKi into frontline induction therapy is a promising strategy for ND PCNS-LBCL.

The patient was treated with Pola-R-CHP followed by CNS-directed therapy, including high-dose methotrexate and intrathecal chemotherapy...Tumor-associated RANKL expression may be associated with the osteolytic features observed in this case. Early biopsy and systemic evaluation of cutaneous lesions are essential, as they may reflect aggressive systemic disease.

The patient was then initiated on combination therapy with carboplatin (area under the curve 5), pemetrexed (500 mg/m2), and osimertinib (80 mg), completing six cycles. Although limited to a single case, our findings support the growing interest in combining systemic and local therapies in EGFR-mutant non-small cell lung cancer and offer a potential framework for adapting these strategies to molecularly analogous tumors. Longer-term follow-up and further studies are needed to refine patient selection and optimize treatment intensity.

This case highlights the diagnostic challenges of antibody-negative paraneoplastic neurologic syndromes. The study underscores the important role of PET-CT in identifying occult malignancy and the role of repeat biopsy in progressive disease. Discordant histologic findings should be interpreted cautiously, as they may reflect tumor heterogeneity or possible adenosquamous carcinoma rather than true histologic evolution. Limited molecular testing, and sampling constraints remain important challenges, particularly in resource-limited settings.

ACT was not significantly associated with improved RFS for stage IA LUADmp patients postoperatively. This study was registered at ClinicalTrials.gov: NCT03351842.

Structure-function drug screening of FDA-approved agents blocking IQGAP3-SOX2 binding identifies trimetrexate as a brain penetrant pharmacologic disruptor of IQGAP3 function in radioresistance, sensitizing GSCs to radiotherapy. These results identify molecular underpinnings for biomechanical promotion of cancer stem cell maintenance and therapeutic resistance, informing therapeutic strategies to augment efficacy of radiotherapy.

Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.