Non-Small cell lung cancer brain metastases treatment [Neurosurgery Wiki]

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====== Non-Small cell lung cancer brain metastases treatment ======

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[[Non-Small cell lung cancer intracranial metastases treatment]].

[[Brain metastases]] are a frequent complication of NSCLC, occurring in ~20–40% of patients. Management depends on:
  * Number and size of metastases
  * Neurological symptoms
  * Molecular profile (EGFR, ALK, ROS1, KRAS, etc.)
  * Performance status (Karnofsky, ECOG)
  * Presence of extracranial disease

===== 1. Initial Assessment =====
  * MRI with contrast – gold standard for diagnosis
  * Staging with PET/CT to assess extracranial burden
  * Molecular testing (EGFR, ALK, ROS1, PD-L1) critical for treatment decision

===== 2. Symptomatic Management =====
  * Dexamethasone – for perilesional edema
  * Antiepileptics – only if seizures present

===== 3. Local Treatments =====

=== a) Stereotactic Radiosurgery (SRS) ===
  * Preferred for ≤10 brain metastases
  * Superior to WBRT in preserving cognitive function
  * May be used after resection of a dominant lesion

=== b) Whole Brain Radiotherapy (WBRT) ===
  * Reserved for patients with multiple (>10), symptomatic, or leptomeningeal disease
  * Associated with neurocognitive decline – use hippocampal avoidance when possible

=== c) Neurosurgery ===
  * Considered for:
    * Single large metastasis with mass effect
    * Need for pathological confirmation
    * Accessible lesion with good performance status

===== 4. Systemic Therapy =====

=== a) EGFR-mutant NSCLC ===
  * Osimertinib (3rd-gen EGFR TKI) – crosses blood–brain barrier (BBB)
  * Active intracranial response rates >70%
  * Osimertinib preferred even in untreated brain mets

=== b) ALK-rearranged NSCLC ===
  * Alectinib, Brigatinib, Lorlatinib – excellent CNS penetration
  * First-line: Alectinib or Lorlatinib (intracranial ORR ~80%)

=== c) ROS1, RET, NTRK rearrangements ===
  * Crizotinib (ROS1), Selpercatinib (RET), Entrectinib (NTRK) – variable CNS activity

=== d) KRAS G12C-mutant NSCLC ===
  * Sotorasib – CNS activity modest, role under evaluation

=== e) PD-L1 positive (≥1%) tumors ===
  * Immunotherapy (e.g. pembrolizumab) ± chemotherapy
  * Limited CNS penetration, but benefit possible with controlled disease

===== 5. Leptomeningeal Disease =====
  * Osimertinib (160 mg) for EGFR+ disease
  * Intrathecal therapy rarely used
  * WBRT may provide palliative benefit

===== 6. Special Considerations =====
  * Antiplatelet therapy may reduce risk of brain metastases (emerging data, see: Martín-Abreu et al., Cancers 2025)
  * Re-irradiation or systemic switch in progression
  * Multidisciplinary tumor board evaluation recommended


====== Antiplatelet Therapy Mitigates Brain Metastasis Risk in Non‑Small Cell Lung Cancer: Insights from a Comprehensive Retrospective Study ======
In a [[retrospective]] [[observational]] [[cohort]]  
Martín‑Abreu et al.  
from the [[Hospital Universitario de Canarias]]
published in the journal [[Cancers]] (Basel)  
to evaluate whether exposure to [[antiplatelet therapy]] reduces the incidence and delays the onset of [[brain metastases]] in patients with [[non‑small cell lung cancer]] (NSCLC).  
Use of antiplatelet agents—mainly [[aspirin]]—was associated with a significantly reduced incidence of brain metastases (6.9% vs. 20.0%), longer metastasis‑free interval (77.5 vs. 62.6 months), improved [[Progression-Free Survival]], and no cases of brain metastasis among those initiating therapy post‑diagnosis
((Martín-Abreu C, García-Gil M, Méndez-Monge M, Fariña-Jerónimo H, Plata-Bello J. Antiplatelet Therapy Mitigates Brain Metastasis Risk in Non-Small Cell Lung Cancer: Insights from a Comprehensive Retrospective Study. Cancers (Basel). 2025 Jun 20;17(13):2059. doi: 10.3390/cancers17132059. PMID: 40647360.)).

=== Critical Review ===
* **Strengths:**  
  * Large sample size (n=650) over 4 years—impressive [[real‑world data]].  
  * Statistically significant findings with p<0.001 for key outcomes.  
  * Stage‑stratified analysis adds biological plausibility.  
* **Weaknesses/Limitations:**  
  * [[Retrospective]] design limits causal inference—confounding by indication is possible; patients on antiplatelet therapy were older with more comorbidities, thus inherently different.  
  * No adjustment details provided for key confounders (e.g., [[systemic therapy]], [[performance status]], [[smoking]] status, brain imaging frequency).  
  * Aspirin dose, adherence, and duration aren’t clearly reported—details crucial for replication.  
  * Follow‑up duration average (~77 months) seems long for advanced NSCLC—they likely included early‑stage cases without clarifying subgroup analysis.  
  * No [[mechanistic]] data; speculative statements about premetastatic niche formation and [[immune evasion]] need validation.

=== Final Verdict ===  
This study delivers intriguing real‑world signals supporting the hypothesis that antiplatelet therapy, particularly aspirin, might reduce the risk or delay brain metastases in NSCLC. However, its retrospective nature, potential [[confounder]]s, and lack of mechanistic clarity significantly limit its impact. Prospective, randomized trials are necessary before changing clinical practice. Meanwhile, it's hypothesis‑generating rather than practice-changing.

=== Takeaway for Practicing Neurosurgeons ===  
Be aware of emerging evidence that low‑cost, ubiquitous drugs like aspirin may modulate metastatic risk. Encourage multidisciplinary collaboration—medical oncology and neurosurgery—to monitor ongoing trials and consider stratifying patients in observational registries by antiplatelet use.

=== Bottom Line ===  
⏤ **Score: 5/10** – [[Thought‑provoking]] with good observational data but not definitive.  
⏤ **Despite interesting associations, limitations in design and confounding preclude recommending routine aspirin use solely for brain met prevention in NSCLC.**