Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation

Radiother Oncol. 2018 Mar;126(3):511-518. doi: 10.1016/j.radonc.2018.01.005. Epub 2018 Feb 3.


Background: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma of the lung who received stereotactic radiation for brain metastases.

Materials/methods: We identified 149 patients with adenocarcinoma of the lung and newly diagnosed brain metastases without a targetable mutation receiving stereotactic radiation. Kaplan-Meier plots and Cox regression were employed to assess whether use of pemetrexed was associated with intracranial disease control and radiation necrosis.

Results: Among the entire cohort, 105 patients received pemetrexed while 44 did not. Among patients who were chemotherapy-naïve, use of pemetrexed (n = 43) versus alternative regimens after stereotactic radiation (n = 24) was associated with a reduced likelihood of developing new brain metastases (HR 0.42, 95% CI 0.22-0.79, p = 0.006) and a reduced need for salvage brain-directed radiation therapy (HR 0.36, 95% CI 0.18-0.73, p = 0.005). Pemetrexed use was associated with increased radiographic necrosis. (HR 2.70, 95% CI 1.09-6.70, p = 0.03).

Conclusions: Patients receiving pemetrexed after brain-directed stereotactic radiation appear to benefit from improved intracranial disease control at the possible expense of radiation-related radiographic necrosis. Whether symptomatic radiation injury occurs more frequently in patients receiving pemetrexed requires further study.

Keywords: Brain metastases; NSCLC; Necrosis; Pemetrexed; Stereotactic.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma of Lung
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Brain / pathology*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Necrosis
  • Pemetrexed / administration & dosage*
  • Radiation Injuries / etiology*
  • Radiation Injuries / pathology
  • Radiosurgery / adverse effects
  • Radiosurgery / methods
  • Retrospective Studies


  • Antineoplastic Agents
  • Pemetrexed