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Kecheng Xu, M.D.*, Lizhi Niu, M.D. Ph.D., Yize Hu, M.D., Weibing He, M.D., Jiansheng Zuo, M.D.
Cryosurgery Center for Cancer, Fuda Cancer Hospital Guangzhou, Guangzhou 510300, China
*Corresponding Author: Kecheng Xu, M.D., Email: xukc@vip.163.com
From February 2001 to July 2007, a total of 3,580 patients with a variety of tumors underwent cryosurgery in Fuda Cancer Hospital of Guangzhou (Table I).
Table I
Cryoablation for 3,580 patients with tumors.
Tumors |
Patients No. |
% |
Lung cancer |
1292 |
31.6 |
Primary liver cancer |
1046 |
29.2 |
Metastatic liver cancer |
329 |
9.2 |
Glioma |
213 |
5.9 |
Tumors of soft tissue |
142 |
3.9 |
Breast cancer |
64 |
1.8 |
Ovary cancer |
61 |
1.7 |
uterine myomas |
54 |
1.5 |
Bone tumors |
53 |
1.5 |
Pancreatic cancer |
51 |
1.4 |
Prostate cancer |
35 |
0.9 |
Renal cancer |
29 |
0.8 |
Skin tumors |
24 |
0.6 |
Anal-rectal cancer |
20 |
0.5 |
Oral tumors |
18 |
0.5 |
Cervical intraepithelial
neoplasia |
16 |
0.4 |
Nasopharengeal cancer |
14 |
0.4 |
Cancer of maxillary sinus |
10 |
0.3 |
Melanoma |
10 |
0.3 |
Parotid cancer |
10 |
0.3 |
Neurofibrinoma |
7 |
0.2 |
Bladder cancer |
7 |
0.2 |
Lymphoma |
7 |
0.2 |
Teratoma |
6 |
0.2 |
Tongue cancer |
7 |
0.2 |
Laryngocarcinoma |
4 |
0.1 |
Other tumors |
45 |
1.3 |
There were 490 patients received intraoperative cryoablation and 3,090 patients received percutaneous cryoablation under guidance of ultrassound and/or CT. A variable number (1-3) of 2 or 3mm cryoprobes were inserted directly into the tumor masses. Generally, lesions smaller than 3cm could be reliably frozen with a single 3mm probe; larger lesions required multiple probes or larger probes (5 or 8mm probes). A double cycles of freeze-thaw procedure were used with an argon gas driven Cryocare Surgical system (Endocare, Inc., USA). Each cryoprobe was first frozen to -160 C and the resulting ice ball was monitored with ultrasound or CT until frozen zones encompassed the entire mass of the tumor with at least one 0.5-1.0cm safe margin. The frozen tissue was then allowed to slowly thaw to 0 C. A second freeze-thaw cycle was then performed after if necessary, adjustment positions of the cryoprobes.
Series of the studies were carried out in various groups of patients with malignant tumors or benign tumors who underwent cryoablation. The results are as follows.
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A total of 1,174 procedures of cryoablation were performed for 840 patients with non-small cell lung cancer (NSCLC). CR was observed in 86 patients (14.4%), PR in 588 patients (70.0%), SD in 115 patients (13.7%) and PD in 51 patients (6.1%). The recurrence rate was 47.2% during a median follow-up of 34 months (range, 4-63). The median survival of all patients was 23 months (range 5-61 months). Overall 1, 2, 3, 4 and 5-year survival rates were 68%, 52%, 34%, 26% and 21% respectively.
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41 patients with obstructive NSCLC were given the combination therapy of percutaneous cryoablation and photodynamic therapy. Bronchoscopy showed that endobronchial tumor had a complete resolution in 41.5 % of patients. CT showed that lung tumor had CR of 34.1% and PR of 41.4%.The 6- and 12-month survival were 44% and 71% respectively.
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50 patients with NSCLC received combination of cryoablation and 125iodine seed implantation. 32 patients were followed-up for 12-41 months, and had 1, 2 and 3-year survival rates of 68%, 43% and 34% respectively. Seven patients are alive for more than 3 years.
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A total of 550 patients with primary liver cancer underwent cryoablation. In them, 152 patients received percutaneous cryoablation alone and were followed-up for 4 years. The tumors in all 152 cases were unresectable. The 1, 2, 3 and 4-year survival rates are 86.4%, 72.9%, 51.6% and 45.4% respectively. The liver cancer smaller than 5cm has better survival rate.
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A total of 326 patients with nonresectable hepatic colorectal metastases underwent percutaneous cryoablation. The cryotreated lesions showed CR 14.6%, PR 41.1%, SD 24.3% and PD 20%. The recurrence rate was 47.2% during a median follow-up of 32 months (range, 7-61). During a median follow-up of 36 months (7-62months), the median survival of all patients was 29 months (range 3-62 months). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5-year respectively after the treatment.
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420 patients with hepatocellular carcinoma received the sequence therapy of transarterial chemoembolization (TACE) and percutaneous cryosurgery. During a mean follow-up of 36±17 months (range 24-60 months). 129 patients (30.7%) showed no evidence of disease, 98 patients (23.3%) were alive with recurrent disease, 170 patients (40.5%) died of disease recurrence or spread, and 23 patients (5.5%) died of other diseases. The overall 1, 2, 3, 4 and 5-year survival rates were 72%, 57.5%, 47%, 39% and 31% respectively. The 4 and 5-year survival rates were significantly higher in patients with TACE-cryosurgery combination than in patients with cryo-alone groups. The local recurrence rate at the ablation area was 17% for all patients, and 11% and 23 % for combination therapy and cryo-alone group respectively (p=0.04). The latter group had more incidences of hepatic bleeding (p=0.02) and liver rupture, while the combination therapy group had more cases of liver failure.
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80 patients with large HCC tumors (>5 cm in diameter) received percutaneous cryoablation followed by repeated ethanol ablation sessions. Results showed that the volume of tumor necrosis initially induced by cryoablation has been significantly increased after adjuvant ethanol ablation sessions. Following ethanol ablation, ultimately, 88.8% of the patients have attained complete necrosis by the end of the protocol (p<0.001). During a median of 26 months (range of 4-67), there were 30 patients (37.5 %) who showed no evidence of disease. Only 4 patients (5.0%) had local recurrence in the cryoablation sites. The 1, 2, 3, 4 and 5-year survival rates were 83%, 64%, 58%, 52% and 43% respectively. Five-year-disease-free survival rate was 27%.
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38 patients with locally advanced pancreatic cancer were considered to be unresectable and underwent cryosurgery, which was performed intraoperatively or percutaneously and 125iodine seed implantation. Eleven patients received intraoperative cryosurgery and 27 patients received percutaneous cryosurgery. Most of the cases had tumor necrosis of different degrees, and CR of tumor was seen in 23.6% of patients. All adverse effects were controlled by medical management with no poor outcome. Median overall survival was 12 months and there were 20 cases (52.6%) whose survival was 12 months or more. Overall 6, 12, 24 and 36-month survival rates were 94.7%, 49.4%, 21.8% and 5.4% respectively. There were 4 cases that had survival of 24 months or more.
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9 patients with renal cell cancer of 1.1-4.2cm (mean 3.2cm) in diameter received percutaneous cryosurgery. During follow-up of 8-38 months, 3 patients died with survival time of 16, 19 and 32 months respectively; 2 patients alive for 12 and 19 months respectively, until the last follow-up; 4 patients are alive with survival of 5-38 months.
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27 patients with single small breast cancer of a median of 13mm with range of 8-25 mm in size underwent percutaneous cryoablation. All patients tolerated the freeze-thaw procedures very well. No viable invasive cancer was discovered in 23 (85.2%) of the 27 patients according to histological findings of specimen from lumpectomy. A ductal carcinoma-in-situ (DCIS) which was present within the normal tissue surrounding the cryoablation zone was discovered in an additional 4 patients (14.8%). 2 of these patients had a small single lesion and 2 cases had multifocal lesions. 11 patients whose tumors smaller than 1.5cm in size were successfully cryoablated with no residual invasive or intraductal carcinoma; whereas the tumors in 4 patients with residual DCIS had 15, 21, 21 and 25mm in size respectively.
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186 patients with glioma underwent an integrated modality consisted of cryosurgery and then immunotherapy of infusing immunomodulation agent into embedded Ommaya capsule, with 1, 2 and 3-year survival rates of 70%, 63% and 54% respectively. 11 patients with higher grades of glioma had 3-year survival rate of as high as 40%.
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There were 8 patients with benign fifroblastoma, 18 fibrosarcoma, 3 teratoma, 1 rhabdomyo-fibroma, 2 neurofibromatosis, 21 liposarcoma, who received intraoperative or percutaneous cryosurgery, with a great improvement in most cases and cured results in some cases.
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42 patients with uterine myomas received percutaneous cryomyolysis. 38 cases were followed-up for 5 to 65 months. 34 cases (89.5%) had shrinkage of tumor masses in various contents.
In summary, as our clinical experiences demonstrated, cryoablation is adapted for treatment of nearly all solid tumors. Percutaneous cryoablation, as a feasible and mini-invasive technique, offers an effective and safe therapy for patients with solid tumors. It is especially suitable for treatment of unresectable advanced tumors.
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