Magic small box adjuvant treatment of lung cancer meningeal metastasis, the disease control rate reached 82.6%

Pia mater metastases (LM) are a "catastrophic complication" of advanced lung adenocarcinoma, with a probability of about 3% to 5%.

The clinical symptoms are manifested as severe headache, intractable nausea and vomiting, etc.
, which seriously affect the quality of life of patients, and the prognosis is very poor, which is a very dangerous complication
.

Treatment of meningeal metastases

The key to treating meningeal metastases is the blood-brain barrier, which must be passed by the drug and reach an effective concentration
.

Intrathecal chemotherapy can deliver drugs directly to the subarachnoid space without passing through the blood-brain barrier, thereby effectively removing cancer cells attached to the meninges, and also has a good killing effect
on cancer cells floating in the cerebrospinal fluid.
However, intrathecal chemotherapy faces some problems, such as the concentration of chemotherapy drugs cannot be too high, so it is necessary to repeatedly perform lumbar punctures, which is easy to cause serious complications
.
In addition, performing a lumbar puncture is also very demanding for the physician
.

Faced with these problems, the researchers found a solution, using the Ommaya reservoir, which is more
effective than repeated lumbar puncture to treat meningeal metastasis.

What is the Ommaya Repository?

The Ommaya Reservoir, invented in 1963 by South Asian-American neurosurgeon Ayub K.
Ommaya
.
As shown in the figure below, the Ommaya reservoir is an intraventricular catheter system that can be used to extract cerebrospinal fluid or deliver drugs into cerebrospinal fluid
.

Figure 1.
Schematic diagram of the Ommaya reservoir

The Ommaya reservoir consists of a catheter in the lateral ventricle that is connected to a reservoir implanted under the scalp to treat brain tumors, leukemia, or leptomeningeal metastases
administered intrathecalally.
For palliative care for patients with advanced cancer, an Ommaya reservoir can also be inserted to inject morphine into the ventricles
.

In patients with meningeal metastases, the Ommaya reservoir shows power

From January 2020 to December 2021, this study included a total of 41 patients with lung adenocarcinoma with meningeal metastases, of which 23 patients met the study targets and were admitted to hospital
.
Another 18 patients were excluded
because of fitness scores, refusal to install the Ommaya reservoir, or uncontrollable epilepsy.

The overall picture of the 23 patients admitted to hospital is as follows:

• Median age: 54 years

• Gene mutations: 18 patients had EGFR gene mutations in tumors and 5 had ALK gene mutations
  .
  

• Meningeal metastases: 18 patients detected meningeal lesions by brain and spinal cord MRI, and the other 5 patients could not detect meningeal metastases by imaging, but were confirmed
  by other methods.
  

• Other: 12 patients also had metastases elsewhere in the brain, and 8 of them received radiation therapy
  .
  Neurological symptoms worsened in all 23 patients, and multiple lines of therapy including targeted drugs, systemic chemotherapy, radiotherapy, and antiangiogenic targeted drugs failed
  .
  

After successful installation of the Ommaya reservoir for these patients, chemotherapy was administered through the Ommaya reservoir on days 1 and 8, with pemetrexed at doses ranging from 30 mg to 50 mg, every 3 weeks
.

Figure 2.
Ommaya reservoir for survival data for meningeal metastasis therapy

Of the 23 patients included in the study, the response rate to treatment was 43.
5% (lesion reduction by more than 30%) and the disease control rate was 82.
6% (no progression).

The treatment survival data in Figure 2 show that the median progression-free survival is 6.
3 months and the median overall survival is 9.
5 months
.

Figure 3.
Changes in drug concentrations for chemotherapy in the Ommaya reservoir

As shown in Figure 3 above, chemotherapy is performed through the Ommaya reservoir, and the blood concentration of blood and cerebrospinal fluid has some consistency
.
Although the drug concentration in the cerebrospinal fluid declined rapidly, the drug concentration was still relatively high in the first 8 hours, and the drug concentration
remained stable and low in the future.

In the entire study, only two patients experienced dose-limiting toxicity, and 30 mg of pemetrexed was considered the recommended dose
for chemotherapy.

Revelation and discussion

In the past ten years, excellent targeted drugs have been continuously developed and marketed, helping many lung cancer patients to cross the 5-year or even 10-year survival period
.
In the long battle with cancer, there is the possibility that other complications, such as meningeal metastases, may occur, and this situation prompts us to look for more solutions
.

From the above data, the Ommaya reservoir is relatively effective
for adjuvant therapy in patients with meningeal metastases.
This technology can be used not only for chemotherapy, but also for taking samples for genetic testing, and even for delivering targeted drugs and immunotherapy drugs
.
The Ommaya reservoir appeared in 1963, and with the confirmation of more clinical research data in the later stage, it is believed that this technology will be widely used to benefit more patients
.

Cancer, accompany you to every step of the fight against cancer!

References:

Huiying Li , et al.
, Safety, pharmacokinetic and clinical ac- tivity of intrathecal chemotherapy with pemetrexed via the Ommaya reservoir for leptomeningeal metastases from lung adenocarcinoma: A prospective Phase I study, Clinical Lung Cancer (2022),

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