INTRATUMORAL IMMUNOTHERAPY

What is immunotherapy?
Immunotherapy is one of the the most rapidly developing area of cancer treatment. It has already revolutionized standard care in many tumor types including skin, lung and kidney cancer. A number of methods and drugs have already been approved that may improve the results of cancer therapy, especially in the advanced stages.

Immunotherapy causes immune cells to attack cancer cells more actively, and thus, improves survival rates and treatment success rates. It is usually used systemically via the arm vein but in recent years, a new method in which an immunotherapy drug is injected directly into the tumor has become increasingly popular.

What is intratumoral immunotherapy?
Intratumoral immunotherapy (IT-IT) is the injection of immunostimulating drugs directly into a tumor to enhance specific immune response against the tumor tissue. It has a number of advantages compared to systemic immunotherapy.

1. In systemic immunotherapy, the tumor may create an immunosuppressive environment which may cause resistance. In intratumoral immunotherapy, this barrier may be overcome by direct administration of the agent.

2. Since the drug is directly injected into the tumor, its concentration in the tumor is higher, thus it is more effective than systemic administration.

3. The amount of administered drug is less (generally 10-20% of that of systemic immunotherapy). Thus the side effects are much fewer and milder. This may allow use of multiple immunotherapy drugs in the same session which may enhance immunotherapy.

4. Since the amount of the drug is lower the average cost of treatment also becomes lower.

5. Although intratumoral immunotherapy involves a direct injection of the drug into the tumor site, the effect is not limited to the injected tumor only. It also creates a strong systemic immune response which may affect other tumors and cancer cells in the body. The method works well even at the metastatic stage of cancer.

What is the effect of ablation+immunotherapy?
After percutaneous ablation, a systemic immune response occurs against the tumor by the tumor proteins released into the circulation from the dead tissue. Many studies have shown that this immune response has a synergetic effect with systemic immunotherapy, thus combined use of ablation and immunotherapy is generally desirable. This synergy is absent in surgery as the tumor tissue is removed out of the body.

A further step to enhance the synegy of ablation+immunotherapy may be the use of IT-IT following percutaneous ablation. As stated above, direct administration of immunostimulants into the tumor may increase safety and effectiveness of the immunotherapy while decreasing the overall cost. This strategy may provide the following benefits:

1. Since the immune cells are activated he tumor may shrink faster.
2. The possibility of local tumor recurrence may be reduced.
3. A systemic effect may be created to control metastatic foci of cancer cells, thereby increasing the patient's life expectancy.
4. When administered concomittantly, local immunotherapy may improve the effectiveness of systemic immunotherapeutic drug.

How is intratumoral immunotherapy performed?
As the name of the procedure suggests, this type of immunotherapy involves performing an injection directly into the tumor. This injection can be done via endoscopy, via a catheter in the feeding artery of the tumor (intraarterially) or from the skin (percutaneously).

Although many drugs or substances can be used for immunotherapy, the most effective and preferred agents are immune check-point inhibitors such as pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo) and atezolizumab (Tecentriq). These agents help the body’s immune system recognize the cancerous cells.

Today, doctors are trying to use intratumoral immunotherapy to treat many oncological diseases. Currently, more than one and a half hundred studies are being conducted around the world to evaluate its effectiveness, and promising results have already been obtained.

In our Varisson Radiology Centers, we have been using intratumoral immunotherapy since 2022. Our preferred agents are nivolumab (Opdivo), pembrolizumab (Keytruda) and ipilimumab (Yervoy). We prefer to use intratumoral immunotherapy after percutaneous cryoablation of the target tumor as we believe that this combination may be more beneficial. So far we used ablation+IT-IT combination in soft tissue sarcomas, lung cancers and breast cancers. Since we inject only a small dose of the agent, we dont see any significant side effects whereas we generally see an improved local effect (faster shrinkage, less recurrence) in most patients and a systemic immune response on other tumors in some patients (abscopal effect).