Therapy in the Treatment of
Lung Cancers of Middle and Late Stage

Xin Yu-Ling, Xue Fu-Zhou, Ge Bing-Sheng, Zhao Feng-Rui, Shi Bin, and Zhang Wei (Department of Thoracic Surgery, China-Japan Friendship Hospital,Beijing 100029)

ABSTRACT

Objective To investigate the effect of electrochernical therapy (ECT) in the treatment of middle and late stage lung cancers.

Materials and Methods 386 cases (287 males and 99 females) with middle and late stage cancers were treated with ECT. The oldest was 78 years old and the youngest was 25 with an average age of 51 years. Two hundred and three patients had got squamous cell carcinoma; 138 Aden carcinoma and 45 undifferentiated cancer. Diameters of the cancer were listed as follows: 153 cases were 4.0-6.0 cm, 82 cases 6.1-8.0 cam, 102 cases 8.1-10.0 cm and 49 cases >10.1 cm. In this group, none was at 1 stage, 103 cases were at II stage, 89 cases lIla, 122 cases HIb and 72 cases IV. Among 386 cases, 152 cases (39.4 %) were with hypertension, heart disease etc. Anode and cathode platinum elecirodes were inserted accurately into the tumour mass. Distance between two electrodes was 2-2.5 cm. Electrodes were connected to a special ECT instrument. The current was maintained at 6-8 V and 80-100 mA. 100 coulombs is applied for treating 1 cm diameter of tumour mass.

Resuits Short term effectiveness In 386 cases, 99 cases (25.6 %) were CR, 179 cases (46.4 %) PR, 59 cases (15.3 %) NC and 49 cases (12.7 %). Effective rate (CR +PR) was 72 % (278 cases). Long term effectiveness One to ~ve year survival rates were 86.3 %‚ 76.4 %‚ 58.8 %‚ 39.9 % and 29.5 %‚ respectively.

Couclusion ECT is used easily, effective, safe, less traumatic and makes patients recover quickly. This is a new and effective method to treat patients with tumours who are inoperable and can not receive chemotherapy or radiotherapy.

Key words electrochemical therapy lung cancer

Electrochemical therapy (ECT) is a method to kill tumours by inserting platinum electrodes into the tumour and connecting electrodes to a direct-current instrument. Free chiorine, oxygen and hydrogen are produced due to electrolysis in the tumour tissue. And there is strong alkalinity and acidity appeared at cathode and anode, respectively. All the effects can destroy tumour cells. As early as 1970‘s, ECT has been used to treat malignant tumours. In 1983, B. Nordenström (1) published a manuscript describing systematically the resuits of fundamental experiments and clinical therapeutic effectiveness of ECT.

Since 1987, based on the experiences of B. Nordenström (2), we have made experimental study on ECT and applied it to clinical practice (3). By the end of 1994, more than 6600 cases with various kinds of tumours had been. treated with ECT in about one thousand hospitals in China. The total effective rate (CR + PR) was 60—80 % in different hospitals. At the First International Symposium on ECT of Cancers held in Beijing in 1992, we reported the application ofECT to 2516 cases of various kinds of tumours. The total effective rate was 78.1 % (4).

In this paper, ECT of 386 cases of middle and late stage lung cancers from October 1987 to February 1989 was reported.

Clinical data

Ofthe 386 cases, 287 cases were male and 99 female. The oldest was 78 years old and youngest 25; with an average age of 51 years. The diameters of tumours measured on X-ray film were 4-6 cm in 82 cases, 6.1- 8.0 cm 153 cases, 8.1-10.0 cm 102 cases and >10.1 cm 49 cases. There were 151 patients (39.1 %) bearing tumours >8.0 cm. According to pathological examination, 203 cases belonged to squamous cell carcinoma, 138 Aden carcinoma; and 45 undifferentiated carcinoma. (Table 1)

TNM classification of386 cases included 11103 cases (26.7 %)‚ lIla 89 cases (23.1 %)‚ IlIb 122 cases (31.6%) and IV 72 cases (18.6 %). The number of cases at middle stage (II + lIla =192) was about the same as that oflate stage cases (Ilib + IV =194). (Table 2)

Metastases were more common in cases with lung adenocarcinoma (50.0 %) than that in squamous cell carcinoma (37.5 %) or undifferentiated carcinoma (12.5 %). Through lymphatic system, there were metastases to pleura (21 cases), cervical lymph nodes (18 cases) and liver (6 cases); and through blond stream to bone (16 cases) and chest wall (11 cases).

In the 386 cases, 39 cases had thoracotomy, 32 cases received radiotherapy (over 4000 cGy), 66 cases received chemotherapy three times, and 65 cases received traditional Chinese medicine for 4-6 weeks. All these treatments were of no effect to the patients before they came to have ECT.

As for complications of the 386 cases, there were 39 cases accompanied with hypertension and 41 cases with coronary heart disease, 31 with chronic bronchitis and emphysema (lung vital capacity <40 % of normal value) and 41 with diabetes.

Therapeutic method

Either of the two types of therapeutic instruments was used: (1) Type BK 91A with adjustable voltage, ampere and electricity quantity buttons and devices for presenting time and auto-alarm. (2) Type BK 92A with Computer to control the above functions. In addition there are expert systems with video picture showing the size of tumour, automatic calculation of the number of electrodes and functions for recording, printing and storing data. Flexible sort or hard platinum electrodes were used according to the conditions of tumour location and constitution. Local, subdural or general anaesthesia was used according to patients‘ conditions.

For those cases without thoracotomy, insertion of electrodes was done under X-ray or CT monitoring. A stylet with insulating tubing outside was inserted first into the tumour, then the stylet was withdrawn out. The electrodes then inserted in through the tubing and passing all through the tumour mass. The insulating tubing was, then, used to protected normal tissue against damage by electricity. After insertion of all the electrodes, the patient was asked to lie on bed calmly.

Electrodes were, then, connected to the instrument. Voltage was gradually raised up to the desired voltage and current was raised up accordingly and maintained at 40-60 or 80-100 niA. The effect ofECT with lower amperage (40-60 mA) and longer duration (2-2.5 h) is better than that of ECT with higher amperage (100-150 mA) and shorter duration (1-1.5 h). This is because that electrolysis needs a longer time to destroy turnour tissue. 4V and 20 mA are the minimal limit for ECT. Experimental results showed that about 100 coulomb per 1 cm of diameter of tumour tissue is needed for killing effects. Cicatricial tumours, with less electrolytes in them, need more electricity, while squamous cell carcinomas, with more electrolytes in them, need a lower quantity of electricity.

Our experimental results and clinical experiences showed that the radius of tumour tissue killed area around each electrode is about 2 cm. The distance between electrodes, thus, should not exceed 2.5 cm. Based on the size and shape of tumour, the number of electrodes could be determined. Usually, anodes are placed in the centre and cathodes near the periphery oftumour, with a distance not more than 2 cm to the edge oftumour in order to prevent normal tissue from electricity damage.

Complications of ECT The main complication, when happened, was traumatic pneumothorax occurring usually with the central type of lung cancer or lung cancer with chronic bronchitis and emphysema. The incidence was 14.8 % (57/3 86). In the 57 cases, 25 had their lungs collapsed by more than 1/3, which were treated immediately with pleural cavity drainage; 32 had only small area of pneumothorax with no breathing difficulty, hence, no treatment was given and ECT carried on continuously. As a preventive measure, oxygen breathing and injection of codeine and diazepam to keep patients in a caim condition, could reduce the incidence ofpneumothorax.

Therapeutic effectiveness The therapeutic effectiveness feil into CR, PR, NC and PD according to the standards by WHO in 1978. Short term effectiveness can be seen in Table 3. The total effective rate

72.0 %. And effective order of short term effectiveness is squamous cell carcinoma (83.3 %~. adenocarcinoma (63.8 %) and undifferentiated carcinoma (46.7 %). TNM staging was closely related to short term effectiveness. (Table 4) The effectiveness decreased with the increase ofstage. That of Stage II was 90.3 %‚ III (66 +79/89 + 122 x 100) 68.7 % and IV 55.6 %. There was significant difference between these groups.

The total short term effectiveness decreased as die size of tumour increased. (Table 5) Effective rate for tumours with diameter less than 8 cm ‘~vas 83.4 % (71 + 125/82 + 153 x 100) and that of tumours~ with diameter greater than 8 cm was 54.3 % (64 + 28/102 + 49 x 100). There was significant difference between these two groups.

One to five year survival rates were calculated by Kaplan-Meier‘s method in 1958. There were 53 cases who died within one year. In the remaining 333 cases, 18 were lost after one year. The results were listed in Table 6. One. to five year survival rates were 86.3 %‚ 76.4%, 58.8 %‚ 39.9 % and 29.5 %‚ respectively. Five year survival rate of cases with squainous cell carcinoma is higher than that of cases with adenocarcinoma and undifferentiated carcinoma. There was significant difference between them. Table 7 showed that the survival rates of stages II and IIIa were higher that that offstage IV. While there was no cases of stage IV survived five years. The difference between survival rates of different stages was statistically significant.

The survival rate of cases with tumour diameter of 4.0-8.0 cm, 35.7 % (40 + 44/82 + 153 x 100) was significantly higher than that of cases with tumour diameter longer than 8.1 cm, 19.9 % (30/151)

Factors affecting effectiveness Number of electrodes and quantity of electricity affect short term effectiveness. In 1987 to 1988, 40 cases of Jung cancer with diameter between 4-6 cm were treated by only two electrodes, one anode and one cathode. Electric quantity used was totally 200-300 coulomb. Clinical effectiveness of this group showed that CR accounted for 17.5 % (7/40), PR 32.5 % (13/40) and CR + PR 50.0 %. Animal experiments in 1988 showed that diameter of killing area around each electrode was 2.5 cm and electric quantity needed was 100 coulomb per 1 cm diameter of tumour tissue. Since February 1989, 42 cases of Jung cancer have been treated by ECT with the above data. The effectiveness has been raised markedly with CR 28.6% (12142), Pr 45.2 % (19/42) and CR+ PR 73.8%. There is significant difference between these two groups.

Factors affect long term effectiveness are:(1) the stage of tumour; as shown in Table 4; (2) size of tumour, as shown in Table 5; (3) pathological type of tumour, as shown in Table 6; and (4) the recurrence rate of tumour. In the 386 cases, 99 cases accounted as short term CR. Five years later, 18 cases (18.2 %) died of local recurrence, 21(21.2 %) died of general metastasis, and 60 (60.6 %) survived over 5 years. Of the 179 cases with PR, 55 cases (30.7 %) died of local recurrence, 70 (39.1 %) died of general metastasis and 54 (30.2 %) survived over 5 years.

Discussion An improved method, ECT, was applied for the treatment of386 cases of lung cancer. The short term and long term effectiveness is comparable with that of surgical Operation and better than that of chemo- or radiotherapy. Therapeutic effectiveness of ECT in treating middle stage Jung cancer with no metastasis is good. 72 cases of stage IV lung cancer and remote metastasis have been treated with ECT to eliminate the primary focus. And other therapeutic measures including radio- and/or chemotherapy and traditional Chinese medicines were combined with for the control of remote metastasis. Patients had less suffering and their live might be prolonged. The other therapeutic measures have also been used in combination with ECT for treating cases with tumour size greater than 8 cm. Correct insertion of electrodes, enough electric quantity and therapeutic time are important. Lung cancers that were found to be inoperable during thoracotomy, could be treated with ECT right away. Electrodes, hence, could be inserted wider direct vision. Good effectiveness could be obtained by ECT in treating tumours which are solitary and its size Jess than 8 cm. ECT is, however, a good method to treat late stage cancer patients who are inoperable and not responsive to radio- and/or chemotherapy.

Typical cases

Mr. Wang, a 52 year-locater, R.N. 09803, complained ofchestpain and distress, and bloody spots in sputum in January 1988. Chest X-ray film revealed a big shadow, 9.5 x 11 cm, in the upper lobe of the left Jung. Bronchoscopic examination discovered that the mass obstructed the bronchus of the Jeft upper lobe. Squamous cell carcinoma was diagnosed by pathological examination. (Fig. 1) He could not be operated due to his cor pulmonale. He received ECT in March 1988. 8 electrodes (4 anodes and ~1 cathodes) were inserted transcutaneously. Voltage given was 8 V, Current 95 mA, and electric quantity\ 1000 coulomb. (Fig. 2) After ECT, chest pain and bloody sputum disappeared. Tumour reduced in size~ markedly when he was discharged. Six months later, the tumour disappeared totally. Hi lived well and resumed his work after following up for 5 years. (Fig. 3)

Mr. Cheng, a 45 year-old staff officer, R.N. 890016, complained of left chest pain and distress, and cough in September 1992. Chest X-ray film revealed a shadow, 7.5 x 8.0 cm, in the left lower lobe and a shadow, 1.2 x 1.3 cm, in the right upper lobe. (Fig. 4) Undifferentiated carcinoma was diagnosed by pathological examination. In October 1992, 6 electrodes (2 anodes and 4 cathodes) were inserted into the mass in the left lower lobe. Voltage given was 7.8 V, current 88 am, and electric quantity 800 coulomb. (Fig. 5) The tumour disappeared after ECT. Traditional medicines and FT 207 were given to the patient for 3 months. Tumour in the right upper lobe disappeared also. Two years later, he was found to be well without recurrence. (Fig. 6)

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