Dramatic Response of Leptomeningeal Carcinomatosis to Nivolumab in PD-L1 Highly Expressive Non-small Cell Lung Cancer: A Case Report

Abstract

In a patient who had been diagnosed of located squamous cell lung carcinoma, pneumonectomy, and adjuvant chemotherapy were performed. Brain recurrence and subsequent lung metastatic disease were uncontrolled by neurosurgery, holocranial radiotherapy, and first-line chemotherapy. In August 2015, appearance of leptomeningeal carcinomatosis triggered severe clinical deterioration and threatened the patient's life. Anti-PD1 immune checkpoint inhibitor Nivolumab was initiated in an attempt to stop tumor growth, achieving a spectacular brain and pulmonary complete response and clinical improvement, without serious adverse effects. High expression PD-L1 level (100%) was found in the pathological tissue sample. Nivolumab was maintained for more than 2 years and stopped in December 2017 after 28 months of treatment, with no disease evidence. More than 3 years after its onset, the patient maintains an outstanding PS with complete tumor response and no evidence of disease in last surveillance CT scan and brain MRI.

Keywords: PD-L1; complete response; leptomeningeal carcinomatosis; nivolumab; squamous lung cancer.

Figure 1

Three significant time points of brain disease. (A–C) Left cerebellar metastasis prior to brain surgery (January 2015). (D-F) Leptomeningeal metastasic disease, predominantly left cerebral hemisphere (September 2015). (G–I) Complete brain response with no evidence of leptomeningeal involvement after 3 months of nivolumab treatment (December 2015).

Figure 2

Follow-up of right lung disease before and after immunotherapy. (a) Pulmonary right nodule, suggesting contralateral lung disease. (b) Complete lung response during nivolumab treatment.

Figure 3

Tissue specimen of primary tumor sample and brain metastases. (a) Immunohistochemistry stained with PD-L1 primary antibody (28-8 pharmaDx; Dako) in a pretreated formalinfixed paraffin-embedded tissue of primary lung tumor before treatment, exhibiting strong membrane staining in 100% of tumor cells (20× magnification). (b) Cerebellar tissue specimen after complete resection.

Figure 4

Timeline of events since the diagnosis and summary of administered treatments.