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Treatment of connective tissue sarcomas by local excision followed by radioactive implant
Clin.RadioL(1976) 27, 39-41 TREATMENT OF CONNECTIVE TISSUE SARCOMAS BY LOCAL EXCISION FOLLOWED BY RADIOACTIVE IMPLANT J. E. COLLINS, C. H. P A I N E and F. ELLIS*
From the Department of Radiotherapy, The Churchill Hospital, Headington, Oxford, OX3 7LJ, England Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites.
The intention was to carry out the whole of the necessary radiation by the dose delivered from the implant. In a few cases however a pre-operative dose of up to 2000 rad was given by external radiotherapy. In a few of the cases also the geometry of the implant was not regarded as satisfactory on films taken post-operatively for dosimetry, so that the implant was removed after a less than radical dose had been given, the dose being made up by post-operative external irradiation. When external radiotherapy was combined with interstitial therapy, it was aimed to bring the dose up by this means to maximal normal tissue tolerance at the envelope enclosing the target volume. In this series, ten cases received post-operative external radiotherapy with cobalt-60 for this reason, out of the total of 32 cases implanted. In a few of the recent cases the concept of nominal standard dose was used to decide the dosage of external therapy which it was necessary to add to the dose given to the target volume by implantation. Actual radiation doses throughout the series were somewhat variable, but in general it was usual to calculate for 6000 rad at approximately 0.5 cm from the plane of the implant, as measured at one of the gaps between the middle lines, halfway along the active length of the wires. A thin slab of tissue was therefore irradiated. As an example, one case received 4000rad at 0.5cm opposite the gap between the middle wires from the implantation in an overall time of four days, and this dose was made up by the addition of 3100 rad in six sessions over 17 days with cobalt-60 gamma-rays.
METHODS THE series concerns 32 cases of connective tissue sarcoma treated in Oxford between 1950 and 1970. There were 18 fibrosarcomas and the others included a diversity of histological types. All patients had a local excision of their tumour. Generally speaking, as complete an excision as possible was carried out, including some normal tissue around the actual neoplasm where surgical and anatomical considerations allowed. At the time of operation, whether or not excision appeared to be complete, plastic tubes were implanted to the bed of the tumour in such a geometry as appeared to be indicated by the target volume of the tumour bed which it was desired to irradiate, usually in the form of one or two planes. These plastic tubes were secured with lead discs for subsequent afterloading with radioactive iridium wires (Paine, 1972), or, in some of the earlier cases, with radium needles (Fig. 1A, B). The after-loading technique involves minimal radiation exposure to staff. In carrying out these implants it was of course necessary to have regard to the geometry of the implant when the wound had been closed, not simply that obtaining daring the actual insertion of the tubes. Separation of the radioactive lines was usually 1.0 to 2.5 cm, depending on the size of the implant, and the ends of the implant were usually 'uncrossed' though appropriate allowance for this was subsequently made in the calculation of dose. *Presentaddress: Memorial Hospital for Cancer and Allied Diseases, New York, New York, USA. 39
40
CLINICAL
RADIOLOGY v _ _
Some patients did develop recurrent tumour near the original site after this treatment but because of the localisation of radiation dose inherent in the method, it was sometimes possible to eradicate the disease by a repeated treatment of the same type, as illustrated by the following case history. A 53-year-old woman presented in 1954 with a three-year history of a swelling in the left thigh which was clinically diagnosed as a lipoma. At operation, a tumour adherent to the quadriceps was found and excised. Histology showed a liposarcoma, and as a second procedure a radium implant to the scar was carried out, delivering 6000 rad in seven days at the point calculated. Three days later a recurrence appeared lateral to the original tumour, and this was excised and as a second procedure tantalum-182 wires and radium needles were implanted to the tumour bed, delivering 5500 rad in eight days. Two years afterwards another lump appeared higher in the thigh; this was excised and a radium implant performed at the same operation, delivering 6000 rad in six days. Three years after this a fourth recurrence developed in the inguinal region. This was again excised and radiation was given in the form of radioactive phosphorus in plastic tubes followed by a radium implant to deliver 4000 rad, followed by 400 rad with cobalt gamma-ray therapy. This procedure was followed by ulceration, presumably radionecrotic, but this ulcer healed spontaneously and the patient has remained free from any further recurrence for ten years. RESULTS Eleven of the 32 cases (34%) developed local recurrence, seven of these being successfully treated either by surgery alone or by surgery combined with radiation. Thus there were only four patients (12.5 %) in whom it proved impossible to control the local disease. Nine patients developed distant metastases (six of these also had local recurrence). Our series is quite small and includes a diversity of tumour histology, size, and site, so that precise statistical analysis is not very meaningful. However it seems to compare favourably with other published series both as regards control of local disease and as regards the development of distant metastases and length of survival. Local recurrence rates are reported by various authors as follows: 65 % by Clark et al. (1957), 87% by Shieber and Graham (1962), 53% by Krementz and Shaver (1963), 70-80 % by Van Der Weft-Messing and Van Unnick
FIG. 1
(1965), and 30-42 % (the better results being achieved by wide rather than simple local excision) by Cantin et al. (1968). Five year survival has been calculated at 57 % for those patients treated earlier in the series, but it may turn out to be higher than this as there are five patients who have remained well to date although they were treated less than five years ago. This survival rate is in fact better than that reported in various series in which radical surgery was employed in the hope of preventing distant metastases; Pack and Ariel (1947) achieved a 29 % five-year survival after radical amputation. Shieber and Graham (1962) achieved a 25 % five-year survival, and Clark et al. (1967) a 41% five-year survival, but these groups including patients treated by a variety of procedures. Hardin (1968) treated 13 patients with sarcomas of the extremities by fore-quarter or hind-quarter amputation, and of the ten patients who survived the operation, the mean survival was 66 months. Three patients developed radionecrosis. All had higher doses than the average of about 6000 rad. Interestingly, these three patients all had persistent disease in that two died of distant metastases, and the third eventually required an amputation; viable turnout cells were present in the necrotic tissue. The likelihood of radionecrosis should be miniraised by achievement of good distribution of sources; our newer after-loading methods help this by allowing unhurried construction of the implant. Six patients in whom surgical excision was known to be incomplete have remained free from local recurrence. This lends support to our proposition that radiation has a definite part to play in addition
TREATMENT OF CONNECTIVE TISSUE SARCOMAS BY LOCAL EXCISION to surgery in the treatment of sarcomas, despite their alleged radioresistance. Seven patients were first seen in the Radiotherapy Department with recurrent tumour following simple excision on a previous occasion, and five of these have remained free from any further recurrence after treatment by our method (for periods ranging from 3½ to 10 years). Histological type seems to have little bearing on prognosis. D r R. H. Cowdell has kindly reviewed the histological slides of the fibrosarcomas, and there appeared to be no correlation between their degree of differentiation, and the development of local recurrence or distant metastases. Neither age nor sex were found to correlate with prognosis. A table giving exact details of the histology, site of lesion, and radiation doses for each case is available from the authors on request. DISCUSSION The unique feature of the treatment of this series is that, at the time of the definitive treatment by local excision, either as the initial treatment or at the time of post-surgical recurrence, radioactive sources or tubes for after-loading with such sources were implanted to the area at risk in the immediate neighbourhood of the operative field. It is considered that the implant, giving a dose of radiation just where it is needed in the bed of the tumour, is the essential feature of this technique - not the application of external irradiation. A similar technique has been used in connection with some other tumours (Ellis, 1963; Ellis and Patterson, 1968). The cosmetic results of this treatment are good, with less damage to the normal tissues than is usual with radical doses of external radiotherapy; despite this lack of normal tissue damage, the volume of tissue at greatest risk can be raised to high radiation dosage. Because the implantation is carried out under the same anaesthetic as the operative excision, very little extra discomfort is produced by it. The extent of the local excision can often be considerably less than is needed where the safeguard of irradiation to effective dosage to the tissues surrounding the operative site is not available. In some circumstances this may make the difference between considerable mutilation and virtually normal post-operative anatomy. In conclusion, we suggest that this technique
41
provides good local control of disease with excellent cosmetic results and minimal risk of complications for patients or hazards to staff. It is capable of eradicating residual disease when surgical removal is incomplete. Its most useful application may be in the treatment of tumours whose natural history is that of repeated local recurrence without distant spread, but these are not easily identified in advance, and we would therefore recommend the method for all cases of connective tissue sarcoma in which it is technically possible to carry it out. Although this series is small, it does not suggest that the risk of distant spread is any greater for patients treated in this way than it is for those in whom a radical surgical procedure has been carried out. Acknowledgements. - It is a pleasure to thank our surgical colleagues, who have referred these patients to us, and who have cooperated with us in the joint operative procedure. We should also like to thank Dr R. H. Cowdell for reviewing the histology of all the cases. The work involved in this analysis was supported by a grant from the Cancer Research Fund, Radiotherapy Department, for which we are grateful. Lastly we wish to thank various members of our secretarial staff for their assistance. REFERENCES CANTIN, J., McNEER, G. P., C ~ , F. C. & BOOKER, R. J. (1968). The problem of local recurrence after treatment of soft tissue sarcoma. Annals of Surgery, 168, 47-53. CLARK, R. L., MARTIN, R. G., WHITE, E. C. t~ OLD, J. W. (1957). Clinical aspects of soft-tissue turnouts. Archives of Surgery, 74, 859-870. ELLIS, F. (1963). My philosophy of radiotherapy. British Journal of Radiology, 36, 627-644. ELLIS, F. & PATTERSON, T. J. S. (1968). The treatment of advanced malignant disease by radiotherapy and surgery. British Journal of Plastic Surgery, XXI, 321-328. HARDIN, C. A. (1968). Radical amputation for sarcoma of the extremities including postoperative resection of pulmonary metastasis. Annals of Surgery, 167, 359-366. KREgENTZ, E. T. & SHAVER, J. O. (1963). Behaviour and treatment of soft tissue sarcomas. Annals of Surgery, 157, 770-784. PACK, G. T. & ARIEL, I. M. (1947). Treatment of Cancer and Allied Disease, Vol. VIII. The Soft Somatic Tissues and Bone. Hoeber Medical Division, Harper and Row, New York, Evanston and London. PAINE, C. H. (1972). Modern after-loading methods for interstitial radiotherapy. Clinical Radiology, 23, 263-272. SHIEBER, W. & GRAHAM, P. (1962). An experience with sarcomas of the soft tissues in adults. Surgery, 52, 295-298. VANDER WERE-MEssING, B. & VAN UNNICK, J. A. M. (1965). Fibrosarcoma of the soft tissues. A clinicopathological study. Cancer, 18, 1113-1123.
From the Department of Radiotherapy, The Churchill Hospital, Headington, Oxford, OX3 7LJ, England Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites.
The intention was to carry out the whole of the necessary radiation by the dose delivered from the implant. In a few cases however a pre-operative dose of up to 2000 rad was given by external radiotherapy. In a few of the cases also the geometry of the implant was not regarded as satisfactory on films taken post-operatively for dosimetry, so that the implant was removed after a less than radical dose had been given, the dose being made up by post-operative external irradiation. When external radiotherapy was combined with interstitial therapy, it was aimed to bring the dose up by this means to maximal normal tissue tolerance at the envelope enclosing the target volume. In this series, ten cases received post-operative external radiotherapy with cobalt-60 for this reason, out of the total of 32 cases implanted. In a few of the recent cases the concept of nominal standard dose was used to decide the dosage of external therapy which it was necessary to add to the dose given to the target volume by implantation. Actual radiation doses throughout the series were somewhat variable, but in general it was usual to calculate for 6000 rad at approximately 0.5 cm from the plane of the implant, as measured at one of the gaps between the middle lines, halfway along the active length of the wires. A thin slab of tissue was therefore irradiated. As an example, one case received 4000rad at 0.5cm opposite the gap between the middle wires from the implantation in an overall time of four days, and this dose was made up by the addition of 3100 rad in six sessions over 17 days with cobalt-60 gamma-rays.
METHODS THE series concerns 32 cases of connective tissue sarcoma treated in Oxford between 1950 and 1970. There were 18 fibrosarcomas and the others included a diversity of histological types. All patients had a local excision of their tumour. Generally speaking, as complete an excision as possible was carried out, including some normal tissue around the actual neoplasm where surgical and anatomical considerations allowed. At the time of operation, whether or not excision appeared to be complete, plastic tubes were implanted to the bed of the tumour in such a geometry as appeared to be indicated by the target volume of the tumour bed which it was desired to irradiate, usually in the form of one or two planes. These plastic tubes were secured with lead discs for subsequent afterloading with radioactive iridium wires (Paine, 1972), or, in some of the earlier cases, with radium needles (Fig. 1A, B). The after-loading technique involves minimal radiation exposure to staff. In carrying out these implants it was of course necessary to have regard to the geometry of the implant when the wound had been closed, not simply that obtaining daring the actual insertion of the tubes. Separation of the radioactive lines was usually 1.0 to 2.5 cm, depending on the size of the implant, and the ends of the implant were usually 'uncrossed' though appropriate allowance for this was subsequently made in the calculation of dose. *Presentaddress: Memorial Hospital for Cancer and Allied Diseases, New York, New York, USA. 39
40
CLINICAL
RADIOLOGY v _ _
Some patients did develop recurrent tumour near the original site after this treatment but because of the localisation of radiation dose inherent in the method, it was sometimes possible to eradicate the disease by a repeated treatment of the same type, as illustrated by the following case history. A 53-year-old woman presented in 1954 with a three-year history of a swelling in the left thigh which was clinically diagnosed as a lipoma. At operation, a tumour adherent to the quadriceps was found and excised. Histology showed a liposarcoma, and as a second procedure a radium implant to the scar was carried out, delivering 6000 rad in seven days at the point calculated. Three days later a recurrence appeared lateral to the original tumour, and this was excised and as a second procedure tantalum-182 wires and radium needles were implanted to the tumour bed, delivering 5500 rad in eight days. Two years afterwards another lump appeared higher in the thigh; this was excised and a radium implant performed at the same operation, delivering 6000 rad in six days. Three years after this a fourth recurrence developed in the inguinal region. This was again excised and radiation was given in the form of radioactive phosphorus in plastic tubes followed by a radium implant to deliver 4000 rad, followed by 400 rad with cobalt gamma-ray therapy. This procedure was followed by ulceration, presumably radionecrotic, but this ulcer healed spontaneously and the patient has remained free from any further recurrence for ten years. RESULTS Eleven of the 32 cases (34%) developed local recurrence, seven of these being successfully treated either by surgery alone or by surgery combined with radiation. Thus there were only four patients (12.5 %) in whom it proved impossible to control the local disease. Nine patients developed distant metastases (six of these also had local recurrence). Our series is quite small and includes a diversity of tumour histology, size, and site, so that precise statistical analysis is not very meaningful. However it seems to compare favourably with other published series both as regards control of local disease and as regards the development of distant metastases and length of survival. Local recurrence rates are reported by various authors as follows: 65 % by Clark et al. (1957), 87% by Shieber and Graham (1962), 53% by Krementz and Shaver (1963), 70-80 % by Van Der Weft-Messing and Van Unnick
FIG. 1
(1965), and 30-42 % (the better results being achieved by wide rather than simple local excision) by Cantin et al. (1968). Five year survival has been calculated at 57 % for those patients treated earlier in the series, but it may turn out to be higher than this as there are five patients who have remained well to date although they were treated less than five years ago. This survival rate is in fact better than that reported in various series in which radical surgery was employed in the hope of preventing distant metastases; Pack and Ariel (1947) achieved a 29 % five-year survival after radical amputation. Shieber and Graham (1962) achieved a 25 % five-year survival, and Clark et al. (1967) a 41% five-year survival, but these groups including patients treated by a variety of procedures. Hardin (1968) treated 13 patients with sarcomas of the extremities by fore-quarter or hind-quarter amputation, and of the ten patients who survived the operation, the mean survival was 66 months. Three patients developed radionecrosis. All had higher doses than the average of about 6000 rad. Interestingly, these three patients all had persistent disease in that two died of distant metastases, and the third eventually required an amputation; viable turnout cells were present in the necrotic tissue. The likelihood of radionecrosis should be miniraised by achievement of good distribution of sources; our newer after-loading methods help this by allowing unhurried construction of the implant. Six patients in whom surgical excision was known to be incomplete have remained free from local recurrence. This lends support to our proposition that radiation has a definite part to play in addition
TREATMENT OF CONNECTIVE TISSUE SARCOMAS BY LOCAL EXCISION to surgery in the treatment of sarcomas, despite their alleged radioresistance. Seven patients were first seen in the Radiotherapy Department with recurrent tumour following simple excision on a previous occasion, and five of these have remained free from any further recurrence after treatment by our method (for periods ranging from 3½ to 10 years). Histological type seems to have little bearing on prognosis. D r R. H. Cowdell has kindly reviewed the histological slides of the fibrosarcomas, and there appeared to be no correlation between their degree of differentiation, and the development of local recurrence or distant metastases. Neither age nor sex were found to correlate with prognosis. A table giving exact details of the histology, site of lesion, and radiation doses for each case is available from the authors on request. DISCUSSION The unique feature of the treatment of this series is that, at the time of the definitive treatment by local excision, either as the initial treatment or at the time of post-surgical recurrence, radioactive sources or tubes for after-loading with such sources were implanted to the area at risk in the immediate neighbourhood of the operative field. It is considered that the implant, giving a dose of radiation just where it is needed in the bed of the tumour, is the essential feature of this technique - not the application of external irradiation. A similar technique has been used in connection with some other tumours (Ellis, 1963; Ellis and Patterson, 1968). The cosmetic results of this treatment are good, with less damage to the normal tissues than is usual with radical doses of external radiotherapy; despite this lack of normal tissue damage, the volume of tissue at greatest risk can be raised to high radiation dosage. Because the implantation is carried out under the same anaesthetic as the operative excision, very little extra discomfort is produced by it. The extent of the local excision can often be considerably less than is needed where the safeguard of irradiation to effective dosage to the tissues surrounding the operative site is not available. In some circumstances this may make the difference between considerable mutilation and virtually normal post-operative anatomy. In conclusion, we suggest that this technique
41
provides good local control of disease with excellent cosmetic results and minimal risk of complications for patients or hazards to staff. It is capable of eradicating residual disease when surgical removal is incomplete. Its most useful application may be in the treatment of tumours whose natural history is that of repeated local recurrence without distant spread, but these are not easily identified in advance, and we would therefore recommend the method for all cases of connective tissue sarcoma in which it is technically possible to carry it out. Although this series is small, it does not suggest that the risk of distant spread is any greater for patients treated in this way than it is for those in whom a radical surgical procedure has been carried out. Acknowledgements. - It is a pleasure to thank our surgical colleagues, who have referred these patients to us, and who have cooperated with us in the joint operative procedure. We should also like to thank Dr R. H. Cowdell for reviewing the histology of all the cases. The work involved in this analysis was supported by a grant from the Cancer Research Fund, Radiotherapy Department, for which we are grateful. Lastly we wish to thank various members of our secretarial staff for their assistance. REFERENCES CANTIN, J., McNEER, G. P., C ~ , F. C. & BOOKER, R. J. (1968). The problem of local recurrence after treatment of soft tissue sarcoma. Annals of Surgery, 168, 47-53. CLARK, R. L., MARTIN, R. G., WHITE, E. C. t~ OLD, J. W. (1957). Clinical aspects of soft-tissue turnouts. Archives of Surgery, 74, 859-870. ELLIS, F. (1963). My philosophy of radiotherapy. British Journal of Radiology, 36, 627-644. ELLIS, F. & PATTERSON, T. J. S. (1968). The treatment of advanced malignant disease by radiotherapy and surgery. British Journal of Plastic Surgery, XXI, 321-328. HARDIN, C. A. (1968). Radical amputation for sarcoma of the extremities including postoperative resection of pulmonary metastasis. Annals of Surgery, 167, 359-366. KREgENTZ, E. T. & SHAVER, J. O. (1963). Behaviour and treatment of soft tissue sarcomas. Annals of Surgery, 157, 770-784. PACK, G. T. & ARIEL, I. M. (1947). Treatment of Cancer and Allied Disease, Vol. VIII. The Soft Somatic Tissues and Bone. Hoeber Medical Division, Harper and Row, New York, Evanston and London. PAINE, C. H. (1972). Modern after-loading methods for interstitial radiotherapy. Clinical Radiology, 23, 263-272. SHIEBER, W. & GRAHAM, P. (1962). An experience with sarcomas of the soft tissues in adults. Surgery, 52, 295-298. VANDER WERE-MEssING, B. & VAN UNNICK, J. A. M. (1965). Fibrosarcoma of the soft tissues. A clinicopathological study. Cancer, 18, 1113-1123.