Inetrnational Journal of Modern Cancer Therapy.2002 (in press)

Oncology Center of PLA, Zhujiang Hospital, Guangzhou, China

How to destroy the tumor tissue quickly and release the patients with cancer from tumor inhibition and painful situation? How to increase the life span of cancer patient using a therapy with feasible, effective, less hurt and less side effect? With the development of Cryocare surgery system, a new targeted ablation therapy has been successfully used to treat lung, liver, breast, brain, and prostate tumors recent years(1-2). About 1500 cases of cancer patients have received this new targeted therapy from October 1999 to March 2002 in China according to the account of China Collaboration Group for Argon-Helium Targeted Cryoablation Therapy(1, 3-9). The quality of life was improved obviously in all the treated patients and the short-term effect was prominent following up by collaboration group doctors. The applications of Cryocare surgery system has promoted the development of tumor targeted therapy and clinical oncology progress.

Cryocare surgery system : A new technology for tumor micro-wound surgery
Cryosurgery System is manufactured by American Endocare Corporation. Using insert-type cryoprobes, it can form an iceball of 3cm to 8cm in diameter to destroy the target tissue and induce necrosis and apoptosis of tumor cells. With these insert-type cryoprobes, cancer surgeon can take targeted ablation tumor tissue with a higher resection rate, and isovolumetric resection tumor tissue without tumor cell transferation during operation. Using targeted cryoablation tumor tissue can modulate anti-tumor immunological response, suggesting a new concept of immunological surgery. Targeted ablation therapy with Cryocare surgery system provide a new technology for tumor micro-wound surgery.
While radical resection remains the first systemic treatment modality for tumor at present, the best chance of radical operation in 60~70% or more cancer patients has been missed when diagnosed. The most commonly causes included: regular operation of the heavy tumor burden influences normal organ function; poor performance status; heart or lung dysfunction of patient can not tolerate any big operation (such as thoracotomy, laparotomy). The micro-wound physical therapy intention of completely destroy the tumor cells and eliminate the tumor burden, had provided a new method for cancer patients. Ar-He targeted cryosurgery system has the advantage of little wound, quick remission, and little influence on vital organs. Cryosurgery procedure can be operated under the guidance of B-type ultrasonography, celioscope, thorascope. Percutaneous targeted cryosurgery can also be done under the guidance of B-type ultrasonography, CT, MR, simulation X-ray localizer and x-ray. Most solid tumor ranged from 5cm to 10cm can be treated with targeted ablation therapy to destroy the tumor through endocare surgery system. The formed ice-ball is 1cm to 1.5cm exceed the border as image showed. For those primary cancer patients without extensive metastasis and local metastatic patients, and can't tolerate regular operation or reject to be operated, Ar-He targeted cryosurgery is a perfect choice. Cryosurgery need not remove the frozen tumor tissue. The advantages include easy manipulation, little complications and quickly clinical effect.

Palliative cryoablation can enhance the effects of systemic therapy
A. lower dosage of chemotherapy.
B. lower dosage of radiotherapy.
C. lessen side effects and improve quality of life.
Indications of targeted ablation therapy are enumerated as follows. Tumors located near big vessels, bile duct, trachea, nerve or vital organ are difficult to be radical resected and radical cryosurgery. Huge tumor complicated light organ function decompensation can't tolerate great operation and cryosurgery. Palliative cryosurgery is the indication for those intention of just lessening tumor volume or load. Cryosurgery once or multiple times for tumor body can achieve part remission, lighten tumor depletion, lessening pain, and improvement of quality of life. Systemic therapy after cryosurgery looks more important for those residual focus, subclinical focus difficulty to be found by image examinations. Clinical studies reveals that drug injection (such as low content acetic acid and sodium hydroxide, high osmotic saline, alcohol, chemotherapeutical drugs) at residual focus will enhance the effects of cryoablation. Some doctors suggest that palliative cryosurgery will decrease the dosage, shorten the time limit, and reduce their complications of radiotherapy and chemotherapy. The attitude in treating multi- focus either primary or metastatic are different. The majority literate believe that do our best to lighten tumor load if patient can tolerate, is benefit to reinforce the curative effects of systemic treatment. Treating with subclinical focus and latent residual tumor cells, palliative cryosurgery must combinate with other systemic therapy.
Further study is needed on how to improve the clinical effects of chemotherapy and radiotherapy with the help of local cryoabalation. How to prevent local relapse and distant metastasis is still a keystone in clinical oncology.

Conformal plan and accurate localization, key step of radical cryoablation
Destroying the tumor rapidly and accurately is the characterization of Ar-He targeted ablation therapy obviously. Without reference to the tumor size and shape, single or multi- time treatment, the formed ice-ball must cover the whole tumor. Most doctors believed the ice-ball encroach 1cm over run the tumor in image might guarantee inactivating tumor tissue completely. To reduce the residual of tumor cells in a great extent is a key step in preventing local relapse and improving curative effects. Conformal cryosurgery can be done during surgery operation under the guidance of B-type ultrasonography or CT in multi- dimensions and angles. In percutaneous cryoablation, curative effects are correlated with monitoring condition and doctors' proficiency, experience, but conformal plan and accuracy localization are most crucial. So it is very important to utilize temperature assay probes exactly, master image diagnosis and have skillful monitoring experience.

Curative effect evaluation and clinical research expectation
Ar-He targeted cryoablation is a local physical technology of destroying tumor tissue directly. The curative effect evaluation of short term mainly depends on the tumor volume decrease, symptoms improvement and laboratory index variation. The difference between Ar-He cryosurgery and regular operation is the former doesn't remove the inactivating tumor tissue by freezing. The great difference between regular radiotherapy and chemotherapy and cryosurgery is the latter can destroy tumor cells rapidly, but the absorption of the cryogenic necrotic tissues is a slow process. Therefore, judge the curative effects from the changes of tumor size and shape is incomprehensive. The curative effects are judged from the changes of the size of iceball and tumor, CT value and blood vessel density in the target area pre- & post- operation(3-8). 1. Clinical complete remission: for cryosurgery ablation therapy patients, the iceball is 1cm to 1.5cm or more beyond the tumor border, postoperative CT or MRI examination registers the disappear of tumor; or the tumor shrinkage prominently post-operation, image confirmation the tumor become into inactivating tissue and lost its multiplication ability with lower density, no or little blood vessel, low CT value or MR signal; no new focus appear maintenance for more than one month, clinical symptoms disappear, body weight increases, tumor marker lower to normal level, quality of life improved prominently or bring back to normal. 2. Clinical partial remission: Palliative targeted ablation therapy patients, the freezing area occupying more than 50% in total volume, CT or MR reveals the disappear of the frozen tumor; or shrinkage obviously. The residual tumor stop growing, no new lesion appears for more than one month, clinical symptoms improved, tumor marker lowered distinctly, quality of life improved prominently. 3. No change. palliative targeted ablation therapy patients, the freezing area occupying less than 50% in total volume, CT or MR reveals the disappear of the frozen tumor; or shrinkage obviously. The residual tumor grow less than 25% in volume, no new lesion appear, clinical symptoms and quality of life without prominent improvement, tumor marker lower little. 4. Progression. Part palliative targeted ablation therapy patients, the freezing volume shrinkage little, and CT or MR showes new proliferative property. The residual tumor grow more than 25% in volume, and with new lesion appear, clinical symptoms progress and quality of life keep down.
Curative effects evaluation in the long future rely on the analysis of materials acquired from follow-up study about local relapse rate, distant metastasis rate, mean survival time, median survival time, survival rate, quality of life. Ar-He cryosurgery system is a product of the development of low temperature medicine. It is a physical therapeutical method that can destroy tumor rapidly like operation. With widely developing of targeted cryoablation therapy in clinical oncology, the project and period of treatment of traditional radiotherapy and chemotherapy would be changed. How to understand and evaluate the significance of targeted cryoablation therapy in clinical oncology practice? How to design the assistant radiotherapy and chemotherapy plan after targeted cryoablation therapy? How to combine cryosurgery together with systemic therapy reasonablly? How to comprehend cryosurgery modulates cell immunology and its molecular biological mechanism? How to design the best targeted cryosurgery plan and disciplines for every kind of cancer? How about the regularity of tumor-related biological marker changing and its significance after cryosurgery? All the questions mentioned above are the topics of collaboration group in the future. These achievements of clinical studies will greatly accelerate the development of low temperature medicine, and promote the development of tumor therapy and clinical oncology progress. Some basic principles like randomization, contrast, repeat and balance must be followed in designing clinical trial.

References

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