Cryoablation is a minimally invasive technique that has shown promise in patients with non-small cell lung cancer (NSCLC), as well as in those with a limited number of small pulmonary metastases. Cryoablation is limited to situations in which surgical resection is not an option due to advanced age and/or coexistent medical morbidities.
Other treatment options in these settings include external beam radiation therapy (RT), stereotactic body radiotherapy, or radiofrequency ablation (RFA). These approaches may result in clinically useful symptom palliation and improvements in survival. However, not all patients have access to these treatments and many may not be candidates due to medical comorbidities. (See "Stereotactic body radiation therapy: Rationale and clinical experience" and "Radiofrequency ablation of lung tumors".)
The mechanisms of cellular cytotoxicity, the techniques of cryoablation therapy, and the early results with this technique are reviewed here. The management of patients with early stage NSCLC and the role of surgery in patients with lung metastases are discussed elsewhere. (See "Management of stage I and stage II non-small cell lung cancer" and "Surgical resection of pulmonary metastases: Outcomes by histology" and "Surgical resection of pulmonary metastases: Benefits; indications; preoperative evaluation and techniques".)
MECHANISMS OF CYTOTOXICITY
The mechanisms of cellular destruction caused by cryotherapy include direct effects on tumor cells and indirect effects on tumor vasculature, both of which can contribute to coagulative necrosis in a tumor .
- When tissue is cooled rapidly, water cannot move out of the cell and there is intracellular ice formation, leading to further intracellular cooling and disruption of enzyme and cell membrane functions. If the temperature is kept low for a period of time, additional crystallization results, further damaging the cell.
- When there is slower cooling of tissue, ice forms in the extracellular matrix, creating a relatively hypertonic environment. Water thus leaves the cell by osmosis, causing intracellular dehydration. During the thawing process the water returns to the cell rapidly, resulting in lysis.
- Indirect damage to the tumor can be due to damage to the tumor's vascular supply. Direct damage to the small vessel walls can occur by the same cellular mechanisms that damage tumor cells. In addition, the small vessels near the tumor can swell during the freezing process, resulting in stasis. Following thawing, reperfusion injury may occur. These indirect effects are only seen in small blood vessels (<3 mm). Larger blood vessels are protected from injury by the effects of blood flow.