Case presentation: (Leptomeningeal metastasis)         April 16, 2016

31 yrs female, FH negative, Known case of Rt breast cancer (3 yrs ago)

2013: BCS & SLNB+ Chemotherapy & RT
        (IDC, G 2, size 2 cm, margin free, LVI - , PNI - , ER + , HER2 - ) 

2014: Wide spread bone mets (throughout spines, ribes, both                  
        shoulders, both humerus, pelvis, both hips and
 both femors with
         C1,C2 & T9,T10 cord
 compression);
Bone radiation

2015: Liver mets; Chemotherapy

2016: Carcinomatosis meningitis ( Meningeal clivus & Spine meningeal         involvement in MRI )

Question: Plan of treatment?

Joint recommendation: Intrathecal chemotherapy

Reference:

1-Jay R Harris,Monica Moro.”Diseases of the breast”. 5th ed. ,2014

Pages 1032-1039: Leptomeningeal metastasis (LM) occurs when tumor spreads to the subarachnoid space and cerebrospinal fluid (CSF) that surround the brain and spinal cord. The frequency of LM in clinical series of patients with breast cancer is estimated at 8%. CNS metastases in breast cancer have been associated with younger age, premenopausal status, infiltrating ductal histology, estrogen- and progesterone-receptor negativity, aneuploidy, altered p53, and epidermal growth factor receptor (EGFR) overexpression (6). Lobular type breast cancer has a predilection for LM compared to other histologic types of breast cancer, LM to occur in 14% of all cases of lobular carcinoma.

Pathologic evidence suggests several methods by which tumor cells reach the leptomeninges:

1. Hematogenous spread to the vessels of the arachnoid or to the choroid plexus of the ventricles,

2. Direct extension from adjacent metastasis in the cerebral parenchyma or dura or the lymphatic paraspinal region;

3. Retrograde access to the subarachnoid space by tumor cells infiltrating the venous system from adjacent calvarial or spinal metastases; or

4. Iatrogenic spread after resection of a brain metastasis.

Symptoms and Signs of Leptomeningeal Metastases: Headache, Mental change, Nausea and vomiting, Gait difficulty, Visual loss, Diplopia, Hearing loss, Dysphagia, Pain, Paresthesias, Limb weakness.

Diagnosis of Leptomeningeal Metastases:

-Neuroimaging: MRI or CT (Gadolinium-enhanced MRI should be the first test  for a patient with

cancer who has new neurologic symptoms),

-Cerebrospinal fluid: Positive cytology, Tumor markers( CA-15-3, CEA), Circulating tumor cells,

biomarkers of angiogenesis (VEGF, tPA)

Treatment: Corticosteroids are usually ineffective in reversing neurologic deficits from LM because there is little edema in the underlying CNS parenchyma. General principles in treatment of LM are implementation of radiotherapy (RT), intrathecal chemotherapy, and systemic chemotherapy.

RT is usually the most effective modality for treating focal LM nodules. It is also the most reliable modality for the relief of symptoms such as cauda equine syndrome and pain. Complete neuraxis RT is discouraged even for diffuse bulky tumor because it does not control the disease and is associated with acute morbidities such as esophagitis and severe myelosuppression. Whole brain RT can enhance the neurotoxicity of chemotherapy administered into the CSF and should be reserved for patients with symptoms from the brain or cranial nerves.

Intrathecal chemotherapy should not be administered concurrently with whole brain RT to reduce the risk of neurotoxicity. Intra-CSF instillation often reduces or spares systemic toxicity, although the CSF can act as a reservoir for some drugs, such as methotrexate, that can slowly leak into the peripheral circulation and cause mucositis and myelosuppression.

Prognosis: The median survival in patients with untreated LM is 1.5 to 2 months although some

survive for years with vigorous treatment. Systemic and intrathecal chemotherapy are the only treatment modalities shown to improve survival in LM when compared to spinal and whole brain RT.

2-NCCN guideline 2016 :

Page 128: Patients with metastatic breast cancer frequently developed many anatomically localized problems that may benefit from local irradiation, surgery, or regional chemotherapy (eg, intrathecal methotrexate for leptomeningeal carcinomatosis).

 

 

 

 





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