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Cryoablation therapy for the treatment of Cancer

Cancer is a term used for a group of diseases where body cells become abnormal exhibiting characteristics such as self-sufficiency from normal body growth signals and insensitivity to anti- growth signals from the body 1. This combined with the cancer cells unlimited replicative potential, its evasion of the body’s attempts to kill the it via apoptosis, its sustained angiogenesis that keeps the tumor nourished, lead to the progression of the cancer 1.

It is no surprise then that the disease burden of cancer is very high with it being the second leading cause for death globally after cardiovascular diseases 2. Unsurprisingly, there are several different therapies for treating cancer. The type of treatment administered usually depends on the advancement of the cancer or the stage or grade of the cancer. Most people end up using a combination of treatments to manage their cancer. Some of these therapies include surgery, chemotherapy, radiation therapy, immunotherapy and hormone therapy.

Cryoablation is also one of these therapies. It is a developing medical solution which involves the use of extremely low temperatures to kill cancer cells, while there are other methods of ablating cancer cells such as radiofrequency ablation, laser interstitial therapy, high-intensity focused ultrasound surgery, and focused microwave thermotherapy, there has been a recent upsurge interest in using cryoablation in the treatment of cancer 3. It has been used in the treatment of a diverse range of cancer types including breast cancer, renal cell carcinoma, prostate cancer, bone cancer, cervical cancer, lung cancer, skin cancer and colorectal cancer 4.

This is because cryoablation is seen as a credible alternative to regular surgery to remove tumors. Firstly, it can be carried out under local anesthesia and conscious sedation 5. Secondly, the patient can go home on the same day as the procedure 5. It is also significantly less invasive, as it does not require significant surgical incisions, which makes it aesthetically pleasing compared to resection of tissue as there is minimal exterior scaring 5. Due to this, the risks of surgical complications such as bleeding and infection are avoided 5. It also does not affect or interrupt the systemic treatment of the cancer via chemotherapy, which is a mainstay of treatment 5.

This method is based upon the use of medical imaging tools such as mammograms in the case of breast cancer, ultrasounds, computerized tomography scans (CT scans) and magnetic resonance imaging scans (MRI scans) 6. They allow physicians to precisely locate the tumor within the tissue and to calculate how much of the tissue will be ablated to ensure complete tumor death. The calculation is necessary as there is an additional 1cm usually added to the size of the tumor to ensure complete ablation 7. This means patients must undergo imaging work-up before the procedure commences.

Cryoablation is usually performed on primary tumors to help reduce the metastatic potential the cancer 4. Cryoablation works because the cytotoxic effects of cold causes the destruction of the tumor cell structure, causing tumor necrosis. This occurs at temperatures lower than -20°C 4.

Using the medical imaging tools to locate the tumor as described above, physicians make a small incision of about 1-2mm and insert the “ablation needle” or cryoprobe through the patient’s skin into the tumor 8. Then the cryoablation machine delivers liquified gas such as nitrogen or argon through the cryoprobe into the tumor which expands into a gaseous state which creates sub- freezing temperatures as low as -190°C causing the tumor and its surrounding areas to form an ice ball or to be frozen 8. This is confirmed using the relevant medical imaging tool. The tumor is usually ablated using freeze and thaw cycles to ensure complete cell death within the tumor 8. The thawing is usually done by replacing the liquified gas with helium or heating the needle internally 4. There are

usually two cycles per treatment. This takes less than an hour. Once the treatment is done, scans are done to check for complications and the patient is placed on a wide-spectrum antibiotic therapy for a few days 5. This makes it a very cost-effective alternative to surgery 9.

Cryoablation induces cancer cell death by apoptosis and necrosis 4. An advantage of cryoablation therapy for cancer cells is that after the tumor cell is killed the intracellular contents are preserved, while also releasing several factors that attract immune cells to the site of cell death 4. The intracellular contents of the cancerous cells are recognized by the immune system, which can lead to a tumor-specific immune response against the cancer 4. This is important in patients where the cancer has metastasized or spread.

References
1. Fouad, Y. A.; Aanei, C., Revisiting the hallmarks of cancer. Am J Cancer Res 2017, 7 (5), 1016-

1036.

2. Global Burden of Disease Cancer, C., Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease StudyGlobal Burden of Cancer, 1990 to 2016Global Burden of Cancer, 1990 to 2016. JAMA Oncology 2018, 4 (11), 1553-1568.

3. Cazzato, R. L.; Garnon, J.; Ramamurthy, N.; Koch, G.; Tsoumakidou, G.; Caudrelier, J.; Arrigoni, F.; Zugaro, L.; Barile, A.; Masciocchi, C.; Gangi, A., Percutaneous image-guided cryoablation: current applications and results in the oncologic field. Med Oncol 2016, 33 (12), 140.

4. Aarts, B.; Klompenhouwer, E.; L. Rice, S.; Imani, F.; Baetens, T.; Bex, A.; Horenblas, S.; Kok, M.; B. A. G. Haanen, J.; G. H. Beets-Tan, R.; M. Gómez, F., Cryoablation and immunotherapy: an overview of evidence on its synergy. Insights into Imaging 2019, 10.

5. Pusceddu, C.; Melis, L.; Ballicu, N.; Meloni, P.; Sanna, V.; Porcu, A.; Fancellu, A., Cryoablation of Primary Breast Cancer in Patients with Metastatic Disease: Considerations Arising from a Single-Centre Data Analysis. Biomed Res Int 2017, 2017, 3839012.

6. Bleyer, A.; Welch, H. G., Effect of three decades of screening mammography on breast- cancer incidence. N Engl J Med 2012, 367 (21), 1998-2005.

7. Baust, J. G.; Gage, A. A., Progress toward optimization of cryosurgery. Technol Cancer Res Treat 2004, 3 (2), 95-101.

8. Mues, A. C.; Landman, J., Results of kidney tumor cryoablation: renal function preservation and oncologic efficacy. World J Urol 2010, 28 (5), 565-70.

9. Chehab, M.; Friedlander, J. A.; Handel, J.; Vartanian, S.; Krishnan, A.; Wong, C. Y.; Korman, H.; Seifman, B.; Ciacci, J., Percutaneous Cryoablation vs Partial Nephrectomy: Cost Comparison of T1a Tumors. J Endourol 2016, 30 (2), 170-6.

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