Straight Dope on Medicine: Put Cancer on Ice

How Cold Is Liquid Nitrogen?

The temperature of liquid nitrogen is −195.79 °C (77 K; −320 °F). This is the boiling point of nitrogen. However, nitrogen can exist as a liquid between 63 K and 77.2 K (-346°F and -320.44°F). Below this temperature, nitrogen forms a solid, while above its boiling point, nitrogen exists as a gas.[i]

Liquid nitrogen is about as cold as you can get. Water becomes a solid at 0°C. That is, if there are no impurities. If there are impurities, you get freezing point depression. That is why you put salt on ice in the driveway, to lower the freezing point by making it impure.

Now apply to tumors.

That is what Ice Cure did, and they are reaping the rewards.[ii]

What’s it like?

That is why we have testimonials.

It is also far less expensive than surgery.

It reportedly leaves no scars and takes less than an hour.

Location, Location, Location

Operating out of CAESAREA, Israel, Ice Cure Medical has picked an idyllic spot.

The ancient city of Caesarea Maritima was constructed during the reign of Herod the Great around 10-9 BC.  The city was fortified by the Romans, early Christians, Muslims, and then again by Christian Crusaders.

The ruins include an amphitheater, a Roman aqueduct, the Herodian hippodrome, and much more.  One of the archaeological finds was a limestone block that featured an inscription noting Pilate.  Pilate is renowned for his part in the crucifixion of Jesus Christ.  This is the only archaeological find featuring his name.

The ancient city ruins are surrounded by beautiful beaches that complement the stunning nature of the archaeological site.  There is also an underwater museum where visitors are able to dive and experience the ruins of the city which are underwater.[iii]

Other Cancers

"The body of clinical data on ProSense continues to grow. Interim results from ICESECRET were recently presented at the Urological Association Conference in Israel which demonstrated ProSense is safe and effective in treating kidney tumors with an 89.5% recurrence-free rate. When filing our De Novo application with the FDA, we submitted the most recent interim ICE3 trial results, which showed there were six cases of ipsilateral breast tumor recurrence ("IBTR") out of 194 patients, or 3.09%. Our commercial and scientific team, including principal investigators of our trials, have been very active presenting, training, and demonstrating ProSense at medical conferences. The high level of interest in ProSense from patients and the medical community is highly encouraging."[iv]

The current gold standard treatment of small renal masses (SRMs) is Nephron-Sparing Surgery (NSS). Cryoablation, percutaneous or laparoscopic, is preferred in patients with multiple comorbidities and technically complex lesions.[v] 

The Machine

I’m sure it’s kosher.

קרח טהור

Release of liquid gases from a high pressure to an atmospheric pressure results in cooling effect and formation of ice crystals, known as the ‘Joule-Thompson’s effect’, the underlying principle of cryoablation.[vi]

Within the same freezing time of 20 minutes, the triple-freeze protocol produced a larger zone of complete necrosis than the dual-freeze protocol, although the length of the zone and cryolesions were similar.[vii]

The Marketplace

Several cryoablation devices have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for use in open, minimally invasive, or endoscopic surgical procedures in the areas of general surgery, urology, gynecology, oncology, neurology, dermatology, proctology, thoracic surgery, and ear, nose, and throat. Examples include:[viii]

• Cryocare® Surgical System (Endocare);

• CryoGen Cryosurgical System (Cryosurgical);

• CryoHit® (Galil Medical) for the treatment of breast fibroadenoma;

• IceSense3™, ProSense™, and MultiSense Systems (IceCure Medical);

• SeedNet™ System (Galil Medical); and

• Visica® System (Sanarus Medical).

Benefits that fly under the radar

Cancer has been known to recur. However, the way in which this is conducted, recurrence stands to be eliminated or tremendously reduced.

Cryoablation is a hypothermic modality exercised as a focal therapy for annihilating cancer lesions. Its application leaves the ablated tumor in situ, allowing multifarious tumor antigens to be available to the host’s immune system. This ensues the activation of innate and adaptive immunity against the tumor antigens. Therefore, cryoablation can be employed as an in vivo vaccination tool to fortify the impact of immunotherapies. Application of checkpoint inhibitors, toll-like receptor agonists, adoptive cell therapies and epigenetic modulators has been shown to galvanize the immune system against tumors. Preliminary data demonstrate an excellent synergy between cryoablation and immunotherapies.[ix]

Tumor removal by surgery does not do this.

Despite all the ablation techniques resulting in an in situ release of tumor antigens, cryoablation stands superior to other techniques in its ability to preserve native antigen structures.[x]

Conclusion

There are definite benefits here over surgery. It is less invasive, quicker and less expensive. The outcomes are also very positive. It won’t be available widely, for now. But it is available. Ice Cure has a handy map to locate centers of operation. Also, it appears that this is intended for “early” stage cancers. We don’t know how it will do with advanced cancers. Their claim is that they have been treating fibroadenomas (benign breast tumors) since 2012.

Cryoablation can also be used for focal sites of metastatic disease. 

The ProSense™ system is a proven solution for the treatment of benign and malignant breast tumors, as well as renal, lung, and bone cancer.

It also appears that combining cryoablation with immunotherapy provides even better outcomes. The goal of immunotherapy is to flag cancer cells as foreign so that they can be recognized by the patient’s own immune system.[xi]

References

[i] https://sciencenotes.org/liquid-nitrogen-temperature-and-facts/

[ii] https://icecure-medical.com/professionals/ice3-trial/

[iii] https://national-parks.org/israel/caesarea

[iv] https://www.biospace.com/article/releases/icecure-medical-announces-preliminary-unaudited-2022-year-end-financial-results-and-amp-recent-operational-highlights/

[v] https://icecure-medical.com/wp-content/uploads/2019/03/Kidney_EUA_poster.pdf

[vi] J. Galon et al. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies, Nat Rev Drug Discov. (2019)

[vii] Kwak K, Yu B, Lewandowski RJ, Kim DH. Recent progress in cryoablation cancer therapy and nanoparticles mediated cryoablation. Theranostics. 2022 Feb 14;12(5):2175-2204.

[viii] https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/cryoablation-of-tumors-located-in-the-kidney-lung-breast-pancreas-or-bone/

[ix] hakradhar Yakkala, Alban Denys, Lana Kandalaft, Rafael Duran, Cryoablation and immunotherapy of cancer,

Current Opinion in Biotechnology, Volume 65, 2020, Pages 60-64, ISSN 0958-1669,

[x] Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity, European Journal of Cancer, Volume 62, 2016, pp. 54-61

[xi] Olagunju A, Forsman T, Ward RC. An update on the use of cryoablation and immunotherapy for breast cancer. Front Immunol. 2022 Oct 27;13:1026475.