THE TREATMENT OF ADVANCED MALIGNANT DISEASE BY RADIOTHERAPY AND SURGERY

Transcription

1 THE TREATMENT OF ADVANCED MALIGNANT DISEASE BY RADIOTHERAPY AND SURGERY By F. ELLIS, M.D., M.Sc., F.R.C.P., F.F.R., and T. J. S. PATTERSON, M.D., M.Chir., F.R.C.S. From the Departments of Radiotherapy and Plastic Surgery, Churchill Hospital, Oxford MALIGNANT disease may be treated by surgery, by radiotherapy, or by a combination of the two. Joint clinics between the plastic surgeon and the radiotherapist allow critical assessment of results after treatment. It is important to have the surgical department sited near the radiotherapy department. Only in this way can urgent consultations be arranged so that a new patient with malignant disease can be seen jointly by surgeon and radiotherapist at his first attendance, and the best form of management planned. Advanced disease can often best be managed by combining radiotherapy and surgery. This paper describes the techniques we have used and the radiobiological principles on which they are based. Advanced disease includes cases in which : (I) surgery or radiotherapy alone is expected to fail because the disease is so advanced when first seen ; (2) surgery has already failed ; (3) radiotherapy has already failed ; (4) radiation damage has been caused; (5) cure is manifestly impossible but ulceration or necrosis is present or imminent. The sufferings, if untreated, of some of these patients can be severe both mentally and physically, and their easement can be a relief to the patient and an encouragement to the medical attendants. The loss of a fungating painful ulcer or a painful fixed mass is worth an operation and two or three weeks in hospital. Such cases often require more effort and ingenuity than early cases, but add little or nothing to survival figures. Their successful treatment depends on intelligent application ofradiobiologicalprinciples. These can be divided into those applying to the treatment of malignant tumours and those applying to the surgery of irradiated tissues : A. Radiobiological Principles applying to the Treatment of Cancer.-- Normal and malignant cells are similarly sensitive to radiation, as shown by experiments in vitro and in vivo (Puck and Marcus, I956 ; Hewitt and Wilson, I959). The proportion of cells killed by the radiation depends on the dose. Normal tissues recover with the aid of a feed-back mechanism and immigration of normal cells, processes which do not apply to malignant turnouts. The greater the number of cells, the greater the number surviving a given dose of radiation, i.e. the bigger the turnout the less the chance of cure. Anoxic cells are less sensitive than oxygenated cells, requiring three times the dose to kill the same proportion. Anoxic cells are present in most malignant turnouts--demonstrable even in turnouts I mm. in diameter (Suit and Maeda, I966). The effective dose of radiation which can be given is limited by the tolerance of the normal tissues. (The "effective dose" depends on dose rate, dose per fraction, number of fractions and total time of the course of irradiation as well as on the dose.) Small volumes of tissue will tolerate larger doses than large volumes. With implanted radium or other radioactive material it is possible to give a larger dose to the same lesion than with external radiation by an X-ray or cobalt beam. 32I

2 322 BRITISH JOURNAL OF PLASTIC SURGERY B. Radiobiological Principles applying to Irradiated Tissues.--Irradiated cells, whether normal or malignant, die at mitosis. The descendants of irradiated cells which have not died in mitosis are capable of indefinite proliferation. In irradiated tissues fibroblasts and capillary endothelial cells may die when they need to proliferate, and the proportion dying is proportional to the effective dose reccived. Repair after incision will not bc possible unless undamaged fibroblasts and other cells are present. Because of this, heavily irradiated tissues cannot repair successfully in the presence of an active infection, and unless there is a good blood supply. Post-radiation conditions may be divided into two groups--acute and chronic--with: in tht acute phase, a good blood supply and irradiated cells; in the chronic phase, poor blood supply, irradiated cells, and post-radiation scarring. The important irradiated cells are the fibroblasts and capillary endothelial cells responsible for repair, and the proportion capable of continued division will depend on the effective Fro. ~ dose given. As time passes capillary blood vessels Free graft to glans penis following radio- in the treated area tend to be obliterated by endotherapy for carcinoma. A man aged 25 thelial proliferation, and scar tissue develops. had a well-differentiated carcinoma which These changes follow more certainly and more had been present for six months. Treat- quickly the larger the effective dose, and they merit was by deep X-rays, followed by a radium applicator. Three weeks after approach completion about six months or more completion of treatment there was no after treatment. The term " effective dose" evidence of tumour present but the glans refers to biological effect. In general, the biolowas denuded of epithelium. The raw surface was covered with a thin split skin graft gical effects are greater (for a dose of a certain from the upper arm ; this took completely, number of rads) the fewer the fractions in which He has remained free of disease for six years, and he has produced two healthy children, it is administered, the shorter the time over which it is administered and the larger the volume treated. Certain surgical principles follow on the above : I. A non-irradiated frcc graft will take on tissue with a good blood supply even if the repair cells of the recipient area have been irradiated (Fig. i). 2. A non-irradiated skin flap will join to tissue with a good blood supply even if this has been irradiated. 3. Dense scar tissue will not accept either form of graft. Methods of combining Radiotherapy and Surgery I. Radiotherapy may be used immediately before operation to reduce the mitotic activity of the tumour so that any cells which are set free by manipulation will be sterile. It is practicable to give 4oo to 50o rads which leaves about I per cent. of cells capable of reproduction. In practice an interval of 24 hours can be administratively convenient as well as being compatible with surgical healing. One of the authors (F. E.) has been using this method for treating carcinoma in many situations, especially

3 TREATMENT OF ADVANCED MALIGNANT DISEASE 323 breasts, since I932. This was based on work by Murphy at the Rockefeller Institute which showed that in mice the irradiation of carcinoma before implantation plus irradiation of the subcutaneous tissue (tumour bed) into which it was implanted was not followed by any growth of carcinoma. This regime was better than irradiation of the tumour bed which was in turn better than irradiation of the tumour only (the reference FIG. 2 Myxofibrosarcoma of the right mandible in a boy of 7. This fungating turnout had grown to its present size in a few weeks. After consultation it was decided that excision of the tumour should be combined with a full course of radiotherapy. Radiotherapy was therefore immediately started. After a carefully calculated dose had been given over 14 days the tumour was smaller ; wide excision was carried out. The wound healed soundly, and radiotherapy was started again Io days after operation. The boy remained well for two years and then died of cerebral metastases. cannot be found.) Rhys Lewis (unpublished) has found 800 rads pre-operatively for breasts to be compatible with primary healing and to give better results than in cases not so treated. Recently Powers and Tollmach (I964) have stressed the desirability of operation immediately after irradiation but this would seem to be unnecessary on theoretical grounds. In the present authors' opinion the most important cause of failure is cells left behind, and therefore post-operative treatment should be given as soon as possible while blood supply is good and before much malignant cell proliferation occurs, provided that primary healing is taking place. 2. Radiotherapy may be used before operation to reduce the bulk of a tumour. 3- Surgery may be used to provide access to a tumour for radiotherapy, e.g. carcinoma of the maxillary antrum is treated first by external radiation ; the palate is then fenestrated and any remaining tumour removed ; the cavity is packed with radium. 4- Surgery, by replacing damaged skin with a healthy flap, will allow furthei radiotherapy to be given to the same area.

4 324 BRITISH JOURNAL OF PLASTIC SURGERY If it has been agreed that an operation will be required as part of combined treatment it is important that it should take place early in the course of radiotherapy. Preliminary radiotherapy will reduce mitotic activity. If the operation is then carefully timed primary healing will not be interfered with, and grafts will "take " normally. The course of radiotherapy can then be continued as soon as the wound has healed (Fig. 2). Combined Treatment of Advanced Malignant Disease.--Combined surgery and radiotherapy have a part to play in the management of advanced malignant disease as defined above. If the surgeon and radiotherapist operate together it may be possible to give acceptable palliation to tumours which are technically inoperable and certainly incurable. In this type of case the disease is very advanced, usually recurrent after a course of radiotherapy, and technically inoperable owing to fixation to vital structures, e.g. a mass of recurrent malignant nodes in the neck which are fixed to the carotid artery. Alternatively, it may be possible to remove the tumour with or without part of the vital structure, but the disease is so extensive that the surgeon is sure that he has not been able to make a complete clearance. The technique to be described allows the radiotherapist to place a source of radiation in direct contact with residual, or suspected residual, turnout. The surgeon has the task of making as complete a clearance as possible of the main tumour mass, and ensuring that there will be healthy skin cover for the defect ; this usually involves the direct transfer of a flap. Technique.--The radiotherapist indicates the area of skin or mucosa irradiated to a high dose. The surgeon removes this area and as much as possible of the main turnout mass, leaving vital structures and inaccessible remnants so that life is not endangered. The surgeon plans and raises a local flap of healthy, non-irradiated tissue which will cover the defect, so that it is possible to see the final disposition of the tissues. The defect is inspected by surgeon and radiotherapist together. The surgeon indicates the parts where there may be residual tumour or where excision has been incomplete. The radiotherapist then plans the arrangement of the radiation source. Polythene tubes which will carry this source are put on or in the suspicious areas and held in place by catgut sutures. It is easier, but not always possible or essential, for both ends of each tube to be brought out in the skin through small stab incisions outside the main suture line. It is important to allow a good length--about 2 inches of free end--and to fix them without producing constriction at the point of passing through the skin, to avoid Lhe ends of the tubes being withdrawn into the tissues. When the tubes have been arranged so that the whole area is covered (usually I'5 cm. apart and parallel when the wound is closed) the flap is sutured into position (Fig. 3). Each tube is threaded with a metallic marker. An X-ray of the area the next day allows the physicist to calculate the dose of radiation required (Fig. 4). Two to three days later, when the wound edges are sealed off, radioactive material (radium or radioactive wire) is introduced into the tubes. When the desirable effective dose has been administered the radioactive material and the plastic tubes are removed (usually 5 to 7 days). This technique is very flexible. If it is not certain whether all malignant tissue has been removed, the tubes can be inserted quite simply, even by the surgeon himself. [flater histology shows that no malignant cells remain the tubes can quickly be removed (Fig. 5). The technique has been used for a number of years. It can be curative, but in all zases it produces good palliation. In particular, pain is relieved.

5 TREATMENT OF ADVANCED MALIGNANT DISEASE 325 A B C FxG. 3 Recurrent fibro-sarcoma of groin in a woman of 80. A, Defect after excision with polythene tubes in place. B, Flap rotated into the defect. C, Suture completed.

6 326 BRITISH JOURNAL OF PLASTIC SURGERY A B C Fro. 4 Secondary node in the neck from carcinoma of the tongue in a woman of 8I. A, The tongue had been treated by radiotherapy one year previously and was clear of disease. Two months after treatment had started a secondary node appeared in the upper deep cervical group. This was irradiated but the node persisted and the overlying skin became ulcerated. B, The tumour was excised. Growth was diffuse and there was doubt about its complete clearance. Polythene tubes were inserted and the defect filled by a transposed scalp flap. X-ray the next day showed the position of metal markers in the tubes. From this the required dose of radiation was calculated, C, The appearance shortly after all tubes had been removed after the required dose of radiation had been g{ven. The radiation source had been in place for five days.

7 TREATMENT OF ADVANCED MALIGNANT DISEASE 327 B C FxG. 5 Recurrent carcinoma of the ca:cum in a woman of 4I. A, Following radiotherapy for recurrence of tumour in the abdominal wall a urinary fistula developed. B~ At operation all irradiated tissue of the abdominal wall was excised. A large mass was found involving the dome of the bladder and a loop of small bowel. The affected area of bladder and 8 in. of ileum were resected. The mass extended to the right wall of the pelvis where the line of clearance was uncertain. Three tubes were inserted with wire markers to allow direct radiation to this area. C~ The abdominal wall was repaired with a rotation flap. Histology showed that no viable tumour tissue was present in any part of the specimen. The polythene tubes were therefore removed.

8 328 BRITISH JOURNAL OF PLASTIC SURGERY SUMMARY The methods of combining surgery and radiotherapy for the treatment of malignant disease are described. The radiobiological principles on which these methods are based are discussed. A new technique is advocated for the treatment of advanced malignant disease. This allows the radiotherapist to place a radiation source in direct contact with residual or inoperable turnout. REFERENCES HEWITT, H. B., and WILSOt% C. W. (1959). Br. ft. Cancer, I3, 675. POWERS, W. E., and TOLLMACH, L. J. (1964). Nature, Lond., 2Ol, 272. PUCK, J. T., and MARCUS, P. T. (1956). ft. exp. Med., IO3, 653- SUIT, M., and MAEDA, M. (1966). Am. ft. Roentg., 96, 177.