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Some radiosensitive bone tumours
RADIOSENSITIVE
BONE
SOME RADIOSENSITIVE BY
ROBERT
TUMOURS
253
BONE TUMOURS
C. TUDWAY,
F.F.R.
RADIOTHERAPIST-IN-CHARGE, RRISTOL ROYAL HOSPITAL
WHEN talking about radiosensitivity it is still necessary to define one's terms. In this paper a radiosensitive tumour is taken to mean one which disappears or grows smaller following a course of irradiation. If the tumour is very radiosensitive then the shrinkage will be immediate and rapid. If the tumour is less sensitive, the shrinkage will be more delayed and possibly less complete. This must not be confused with radiocurability, which refers to the prospect of getting rid of the tumour completely and the avoidance of recurrence at the original site or elsewhere. Usually the curable tumours are those of intermediate sensitivity, but in the case of bone tumours, at least one of the very radiosensitive types is also curable, as we shall see later. The radiosensitive bone tumours are a rather varied group with little in common other than their name, so the whole group will not be dealt with, but only a few particular types where we may have information to contribute or ideas to underline. These are reticulum-cell sarcoma primary in bone, malignant synovioma and multiple myeloma. However, it is necessary to make just one point about osteoclastoma, that is to disagree with the suggestion made elsewhere in this symposiums that surgery should be the first line of attack in this tumour in the majority of cases (Eyre-Brook, i956 ). RETICULOSARCOMA
OF B O N E A N D EWING'N T U M O U R
It is sixteen years since primary reticulum-cell sarcoma of bone was separated from other cases which had been described as Ewing's tumour (Parker and Jackson, I939) , but even recently, some authorities, e.g., Geschickter and Copeland (!949), do not describe reticulosarcoma as a separate entity. I t must be emphasized that the distinction between reticulosarcoma and Ewing's tumour must be made and is most important. Reticulosarcoma of bone is a rare tumour, so the number of cases we have in the Bristol Bone T u m o u r Register is not large, but it is hoped these few cases will help to underline the point that it is a curable disease when it is solitary, whereas Ewing's tumour is rarely curable. T h e r e has been much controversy whether Ewing's tumour has a separate identity or is only one of a mixed group which includes secondary neuroblastoma and different types of reticulosarcoma. U p till now, the Register here has recognized it as a separate tumour, and one with a very bad prognosis, though the patient may survive for two or three years after diagnosis. T h e r e is considerable evidence for labelling most of our Ewing's cases either as neuroblastoma or reticulosarcoma, in which many of the reticulosarcomas are found to be multiple tumours which are clinically different from the true cases of reticulosarcoma primary in bone at one site only. Coley, Higinbotham, and Groesbeck (1954) have studied 44 cases of reticulosarcoma and give the incidence as 5 per cent of malignant bone tumours. T h e y quote 47 per cent five-year cures and 38 per cent ten-year cures in their cases. Coley (1949) advocates surgical excision as the treatment. Lichtenstein (i952) reports a 5 ° per cent cure rate also, b u t he suggests that irradiation may cure these cases. Our experience shows that irradiation is the proper method of radical treatment, and compared with other primary malignant tumours of bone the prognosis is relatively good. Biopsy before treatment is necessary to recognize this tumour. Some may be very radiosensitive so that no irradiation at all should be allowed before biopsy, or the fine histological detail will be lost. Radiotherapy can be started immediately after biopsy and there is no significant danger of producing metastases. Metastases may be late in cases of reticulosarcoma, and the i8
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general condition of the patient remains good in spite of the presence of a large tumour, so that a fully radical approach is usually justified. T h e technique of X-ray treatment involves that the tumour should be widely covered, and 3ooo r given in 3-4 weeks, or, if this is too difficult, 25oo r may suffice. Some cases are much
Fig. z 3 9 . - - R e t i c u l o s a r c o m a p r i m a r y in a vertebra.
Tomo-
Fig. 2 4 o . ~ T h e
g r a p h to show lesion before treatment.
same case as Fig. 239 deep X - r a y treatment.
seven
years
after
more radiosenstive and a lower dose would be enough, b u t unfortunately we have not as yet any means Of distinguishing the more from the less sensitive examples beforehand so we prefer to use the dose mentioned. Opinions may differ in the interpretation of histology so that all solitary tumours, where any suspicion or difficulty of classification arises, should be given radical treatment. If one is working Table / . - - P R I M A R Y R E T I C U L U M - C E L L SARCOMA OF B O N E
(Solitary when first seen.
CASE NO.
Ao~
Accepted as proven diagnosis by Bone Tumour Register. (6 eases)) SEx
II
5I
F.
144 18i 388 39° 397
42
F.
34 3
F. M.
56 71
F. M.
SITE
Femur Cervical spine Humerus Ear Ilium Clavicle
D.X.R. Dose 4000 r 2200 r 3200 r
46oo r IOOO r
3000 r
SURVIVAL TIME RECURRENCE
Treated with deep X rays
DEAD OR ALIVE
FREE
9 yr. 7 yr. 6 yr. 8 ruth. 7 mth. 7 mth.
Alive Alive Alive Dead (atypical case) Dead (secondaries in chest Dead (distant metastases)
RADIOSENSITIVE
BONE
TUMOURS
255
with colleagues who prefer to make no clear distinction between the types and label everything under the omnibus title ' Ewing ', then the only thing to do is to recognize that a proportion of all such Ewing's tumours may be curable and to treat all such solitary growths radically. We have treated secondary neuroblastoma with about the same dosage of" up to 3000 r, and have found that it is definitely less sensitive, and that in two-thirds of the cases only a little temporary relief was given. The cases of reticulosarcoma are listed in Table I. These are all the cases we have which were primary in bone, solitary when seen, and which were treated with deep X rays. Here, unless
Fig. 2 4 I . - - A case of reticulosarcoma of femur at the time of radiotherapy in 1945.
F~g, 242.--The same case as Fig. 24I nine years later. The extent of the abnormal bone is well shown.
the results are to be discarded as the results of chance in a small group, the record is much more hopeful. Half the cases have survived over six years and are apparently cured, and this agrees with the much larger American series. T h e level of dosage is again the same and ranges from 2000-4000 r. Case No. 388 is atypical" in two ways ; the patient was young (3 years), and the dose of 45oo r had only a slow and incomplete effect in making the tumour disappear. Two of the surviving cases are described below. Case I 4 4 . - - I n shoulders.
O c t o b e r , 1 9 4 7 , t h e p a t i e n t , a w o m a n a g e d 42, c o m p l a i n e d o f a s t a b b i n g p a i n b e t w e e n t h e In December a paralysis commenced and by April, 1948, she had an upper motor neurone paralysis
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at the level of D.V. 4, with incontinence of urine and sensation losses. A radiograph (Fig. 239) was thought to show an osteoelastoma but a biopsy of the spinous process of the vertebra showed reticulosarcoma. Treatment with 2200 r was given to the tumour in four weeks in April, 1948. By August there was return of sensation. In November, i948 , bladder control returned accompanied by spasms in the legs. In January, 1949, a tenotomy was performed to relieve the effects of the spasm of the adductors and hamstrings, after which the patient quickly began to walk. She is now walking well seven years later, and her general health is very good. A recent radiograph has shown the bodies of D.V. i and 2 to be fused (Fig. 240). Case i i . - - T h i s female patient was aged 51 years. In 1945 pain commenced in the right leg. rRadiographs showed a tumour of the femur (Fig. 24i ). Biopsy at first reported it to be a Ewing's tumour but scrutiny by the Bone T u m o u r Register gave a definite classification as reticulosarcoma. 4o0o r of deep X rays were given in two courses between September, 1945, and January, I946. Further radiographs in June, i946 , suggested that the lesion had completely healed. There have at no time been any signs of chest secondaries or of recurrence.
Fig. 243.--A tumour of the ilium, diagnosed as Ewing's tumour but probably reticulosarcoma, occurring in a girl of I5. A recent radiograph (Fig. 242) shows that the extent of bone repair is wider than the evidence of tumour in the first radiograph and shows the need to treat a wider field than will just cover the obvious tumour. T h e patient is very well now. T h i s case is a n i n e - y e a r survival and, as well as i l l u s t r a t i n g t h e possibilities of cure, s h o w s h o w s u c h a case t e n d s to h a v e a diagnosis o f E w i n g ' s t u m o u r f a s t e n e d o n to it u n l e s s it is well scrutinized. Lastly, t h e r e is o n e r e m a i n i n g case w h i c h c a m e to us l a b e l l e d E w i n g ' s t u m o u r , b u t u n f o r t u n ately t h e histological m a t e r i a l o n w h i c h t h i s d i a g n o s i s was b a s e d w a s n e v e r available to t h e Register, so this m a l i g n a n t t u r n o u t is n o t firmly classified. I t is, h o w e v e r , a n e x a m p l e of t h e fact t h a t w h e n ever a d i a g n o s i s of E w i n g ' s t u m o u r h a s n o t b e e n g i v e n b y e x p e r t o p i n i o n , k n o w n to h a v e e x c l u d e d o t h e r alternatives, t h e case m u s t be r e g a r d e d as c u r a b l e a n d radically t r e a t e d if possible.
Case 25.~-The patient was a girl of I5 when she came to us in January, 1942. She had had pain in the right hip for four months and was limping. On examination she had a firm mass in the right iliac fossa about I2 cm. in diameter. It was attached to the ilium and the swelling obscured the anterior superior spine. Biopsy had been performed in the Bristol Royal Infirmary one week previously and reported as Ewing's sarcoma. Blood-count and a chest radiograph were normal. T h e r a d i o g r a p h o f t h e pelvis is s h o w n i n Fig. 243, T h e r e is d e s t r u c t i o n of a m a j o r p a r t of t h e r i g h t i l i u m b y a n osteolytic t u m o u r . D e e p X - r a y t r e a t m e n t was s t a r t e d i n J a n u a r y , 1942.
RADIOSENSITIVE
BONE
TUMOURS
257
I5OO r were given in three weeks, widely to the whole area. The mass was very radiosensitive and by the end of treatment was much smaller. A radiograph four months later showed marked repair of the bone, and by April, 1946, bone repair was complete (Fig. 244). Another satisfactory point was that menstrual function had returned after the treatment, and in 1946 the patient was married, and though warned against pregnancy, was delivered in 1948 of
Fig. a 4 4 . - - T h e same t u m o u r as Fig. 243 four years after deep X - r a y treatment, normal pregnancy and delivery.
T h e patient t h e n married and went t h r o u g h She was well I3 years after treatment.
a 61-lb. normal child. A second child was born in 195o. She is still very well thirteen years after treatment. The X-ray dosage was on the low side, but fortunately the tumour was both very radiosensitive and radiocurable. The response to treatment and the long survival is much in favour of a diagnosis of reticulosarcoma.
MALIGNANT SYNOVIOMA We have in the Register only eight cases of this tumour (Table II). Of these patients, four survive at the present moment, but only two of them without recurrence. Both recurrence-free survivors received deep X-ray therapy. One of them is Case No. 176 on the list. The patient arrived with a diagnosis of synovioma already made as a result of a biopsy at the hospital of origin. The clinical evidence, site of tumour, metastases to inguinal glands, and the radiological appearances, were considered compatible with synovioma. Professor Hewer (1956) has reviewed the histology of the case and has accepted it as a clear example of the tumour. Deep X-ray therapy was given up to a high dose, 75oo r being given in nine weeks. At the end of this treatment a deep inguinal gland was found to be enlarged. The gland was excised by Professor Milnes Walker and 3ooo r deep X rays in 2I days were given to the groin. The patient has been very well for 6½ years now with no sign of recurrence since and uses her leg normally. The radiographs of this case appear in the paper by Dr. Ross (Ross, 1956) . The second case treated with deep X rays is a three-year survivor without recurrence. He also was given a high dose of deep X rays which was sufficient to cause radionecrosis, for which the leg had to be amputated.
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T h e third deep X-ray case was given a smaller dose of 35oo r, and here the tumour recurred after four years. T h e patient died with chest secondaries. Three of the cases were treated by local excision of the t u m o u r and have either died of the disease or now have recurrences. I n five cases the site of origin is adjacent to the lower end of the femur and this seems to be the site of election. Four of them had inguinal node metastases. This is only a small group so that one can only give very general indications of the best lines of treatment. One can see that this is indeed a very malignant t u m o u r with a pronounced tendency to Table/L--MALIGNANT SYNOVIOMA
(Cases with record of treatment (8 cases)) i
SITE OF TUMOUR
CASE AGE NO.
METHOD OF TREATMENT
DEAD OR
SURVIVAL TIME
RECURRENCE OR METASTASES
Recurrence locally aftra 3 yr. First local excision, thml glands in groin Secondaries in lung and scapula Chest, and glands in groin Chest, and glands in groin Glands of groin when first treated Nil Local recurrence in 4 yr.: then chest secondaries
ALIVE
421
29
Thumb
Local removal
Alive
3½ yr.
2IO
43
Near upper end of femur
Radical amputation
Dead
5½ yr.
457
58
Patella
Amputation
Dead
16 ruth.
640 63
Near lower end of femur
Local removal
Dead
I½ yr.
597
33
Near lower end of femur
Local removal
Alive
I½ yr.
~76
20
Near lower end of femur
D.X.R. 7500 r in 9 wk.
Alive
6½ yr.
426 89
50 32
Near lower end of femur Near lower end of femur
D.X.R. high dose D.X.R. 35oo r
Alive Dead
3 yr. 5 yr.
spread to both the lungs and the local lymph glands. Local excision is not a reliable treatment. T h e disease is clearly somewhat radiosensitive and responsive to irradiation, and can sometimes be cured by this m e a n s . . There may be an immediate reduction in size of both primary tumour and inguinal nodes, b u t a high dose is likely to be needed for the permanent destruction of the primary. As in the case of all bone tumours, high energy irradiation is the correct form of treatment to use and can be expected to give a greater margin of safety against necrosis than deep X rays when high doses are given. We in Bristol have had to use deep X rays up to the present time. Synovioma is more responsive than the general group of connective-tissue sarcomata, and irradiation should not be dismissed as a primary treatment. It is suggested that radiotherapy, preferably with high energy irradiation, may be used for the first radical attack on the tumour, and the only reliable alternative is amputation. A local excision must always be followe d by radical radiotherapy.
MYELOMATOSIS This is one of the commonest of bone tumours. It is a universally fatal tumour, and we are not in sight of any means of curing it. Treatment is therefore purely palliative. T h e main object in discussing so unpromising a disease is to give the results of the treatment of a few cases with radioactive phosphorus and to suggest that this is a good method of treatment useful in the majority of cases and occasionally producing great benefit. We have complete follow-up records of 47 cases of multiple myeloma to draw upon. I n addition, there are two of probably solitary myeloma. Seventeen of the 47 multiple cases have had treatment with pa2. T h e cases treated by different methods have been separated (Table III).
RADIOSENSITIVE
BONE
TUMOURS
259
T h e average t i m e of survival after pa2 is seen to be one year nine months. T h r e e of t h e cases in fact lived o v e r three years, and three over two years. G o o d relief of pain was o b t a i n e d in most of t h e m , and w e l l - b e i n g and activity were i m p r o v e d . T h e r e are nine cases w h i c h had t r e a t m e n t w i t h deep X rays to those parts of the skeleton w h i c h were p r o d u c i n g pain or other s y m p t o m s . T h e average survival here is only nine months. T h e Table IlL--MULTIPLE MYELOMA CASES
Method of Treatment p32 Deep X rays Surgical excision Stilbamidine None
No. of Cases 17 9 3 i 17
Average Survival Time I yr. 9 ruth. 9 mth. 4 ruth. 4 mth. 2½ mth.
cases were not selected and were similar in type and stage of a d v a n c e m e n t to those treated by p3~. T h e two longest survivals were each j u s t over two years. S e v e n t e e n cases had no t r e a t m e n t other t h a n s y m p t o m a t i c drugs not calculated to damage the t u m o u r . T h e average survival t i m e is only 21 months, b u t h e r e there has inevitably b e e n some selection, as the v e r y ill or dying patients were obviously less likely to be treated and this group is not c o m p a r a b l e w i t h the p32 group. M y o w n p r e s e n t feeling is that some f o r m of generalized t r e a t m e n t m u s t be given to attack this disease all over the b o d y and that, at present, pa~ is the best m e a n s of d o i n g this. It will usually produce a general relief of pain e v e r y w h e r e in the b o d y and significantly increases b o t h the total survival t i m e and, w h a t is also i m p o r t a n t , t h e w e l l - b e i n g and activity of the patient. D e e p X rays should, however, be also used in the same cases to deal f r o m t i m e to t i m e w i t h local r e c u r r e n c e of s y m p t o m s , since the total q u a n t i t y of pa~ used must, in the end, be limited by the tolerance of the bone marrow. T h e radiological appearances after pa~- t r e a t m e n t are, to s o m e extent, misleading, because v e r y little change is usually seen in the radiographs even w h e n relief of s y m p t o m s and i m p r o v e m e n t of activity is m o s t marked. T w o selected cases described b e l o w show the results sometimes obtainable. Case 7135.--A man aged 59 had had his disease nearly two years when, from the level of D.V. 2 and 3, complete paralysis occurred with incontinence of urine. Five mc. of p82 were given more or less as a despairing gesture and the patient sent to a chronic hospital. Two months later, movement of the toes re-appeared ; the improvement continued slowly and in August of that year 5 mc. of W 2 were given. By November, 1951, both legs were moving and his bedsores were healed. In April, I952--one year after the first dose--he was walking with crutches. Unfortunately he later developed heart failure and in April, I953, died with left ventricular failure and h~ematemesis. Case I i2o2.--This case, a woman aged 61, came to us in May, 1952. She was given a dose of 5 inc. of p82. Her white blood-count at that time was 64oo. She lost her pains and became more active. Repeat doses of p32 were given in March, 1953, and January, 1954, 8 inc. and 5 Inc. respectively. She has remained well for three years from then to the present time, except when she fell and hurt herself. Her white count in September, I954, was 3000. REFERENCES COLE'Z, B. L. (1949), Neoplasms of Bone and Related Conditions: Their Etiology, Pathogenesis, Diagnosis, and Treatment. New York : Hoeber. - - - - HIGINBOTHAM, N . L., and GROESBECK,H. P. (I954), Surg. Gynec. Obstet., 99, 142. EYRE-BRooK, A. L. (I956), J. Fan. Radiol., 7, 222. GESCHICKTER, C. F., and COPELAND, M. M. (I949) , Tumors of Bone, 3rd ed. Philadelphia and London: Lippincott. HEWER, T. F. (i956),J. Fac. Radiol., 7, 23o. LICHTENSTEIN, L . ( I 9 5 2 ) , Bone Tumours. London : Henry Kimpton. PARKE~, F., and JACKSON,H. (1939), Surg. Gynec. Obstet., 68, 45. Ross, F. G. M. (1956), ft. Fac. Radiol., 7, 242.
BONE
SOME RADIOSENSITIVE BY
ROBERT
TUMOURS
253
BONE TUMOURS
C. TUDWAY,
F.F.R.
RADIOTHERAPIST-IN-CHARGE, RRISTOL ROYAL HOSPITAL
WHEN talking about radiosensitivity it is still necessary to define one's terms. In this paper a radiosensitive tumour is taken to mean one which disappears or grows smaller following a course of irradiation. If the tumour is very radiosensitive then the shrinkage will be immediate and rapid. If the tumour is less sensitive, the shrinkage will be more delayed and possibly less complete. This must not be confused with radiocurability, which refers to the prospect of getting rid of the tumour completely and the avoidance of recurrence at the original site or elsewhere. Usually the curable tumours are those of intermediate sensitivity, but in the case of bone tumours, at least one of the very radiosensitive types is also curable, as we shall see later. The radiosensitive bone tumours are a rather varied group with little in common other than their name, so the whole group will not be dealt with, but only a few particular types where we may have information to contribute or ideas to underline. These are reticulum-cell sarcoma primary in bone, malignant synovioma and multiple myeloma. However, it is necessary to make just one point about osteoclastoma, that is to disagree with the suggestion made elsewhere in this symposiums that surgery should be the first line of attack in this tumour in the majority of cases (Eyre-Brook, i956 ). RETICULOSARCOMA
OF B O N E A N D EWING'N T U M O U R
It is sixteen years since primary reticulum-cell sarcoma of bone was separated from other cases which had been described as Ewing's tumour (Parker and Jackson, I939) , but even recently, some authorities, e.g., Geschickter and Copeland (!949), do not describe reticulosarcoma as a separate entity. I t must be emphasized that the distinction between reticulosarcoma and Ewing's tumour must be made and is most important. Reticulosarcoma of bone is a rare tumour, so the number of cases we have in the Bristol Bone T u m o u r Register is not large, but it is hoped these few cases will help to underline the point that it is a curable disease when it is solitary, whereas Ewing's tumour is rarely curable. T h e r e has been much controversy whether Ewing's tumour has a separate identity or is only one of a mixed group which includes secondary neuroblastoma and different types of reticulosarcoma. U p till now, the Register here has recognized it as a separate tumour, and one with a very bad prognosis, though the patient may survive for two or three years after diagnosis. T h e r e is considerable evidence for labelling most of our Ewing's cases either as neuroblastoma or reticulosarcoma, in which many of the reticulosarcomas are found to be multiple tumours which are clinically different from the true cases of reticulosarcoma primary in bone at one site only. Coley, Higinbotham, and Groesbeck (1954) have studied 44 cases of reticulosarcoma and give the incidence as 5 per cent of malignant bone tumours. T h e y quote 47 per cent five-year cures and 38 per cent ten-year cures in their cases. Coley (1949) advocates surgical excision as the treatment. Lichtenstein (i952) reports a 5 ° per cent cure rate also, b u t he suggests that irradiation may cure these cases. Our experience shows that irradiation is the proper method of radical treatment, and compared with other primary malignant tumours of bone the prognosis is relatively good. Biopsy before treatment is necessary to recognize this tumour. Some may be very radiosensitive so that no irradiation at all should be allowed before biopsy, or the fine histological detail will be lost. Radiotherapy can be started immediately after biopsy and there is no significant danger of producing metastases. Metastases may be late in cases of reticulosarcoma, and the i8
254
JOURNAL
OF
THE
FACULTY
OF
RADIOLOGISTS
general condition of the patient remains good in spite of the presence of a large tumour, so that a fully radical approach is usually justified. T h e technique of X-ray treatment involves that the tumour should be widely covered, and 3ooo r given in 3-4 weeks, or, if this is too difficult, 25oo r may suffice. Some cases are much
Fig. z 3 9 . - - R e t i c u l o s a r c o m a p r i m a r y in a vertebra.
Tomo-
Fig. 2 4 o . ~ T h e
g r a p h to show lesion before treatment.
same case as Fig. 239 deep X - r a y treatment.
seven
years
after
more radiosenstive and a lower dose would be enough, b u t unfortunately we have not as yet any means Of distinguishing the more from the less sensitive examples beforehand so we prefer to use the dose mentioned. Opinions may differ in the interpretation of histology so that all solitary tumours, where any suspicion or difficulty of classification arises, should be given radical treatment. If one is working Table / . - - P R I M A R Y R E T I C U L U M - C E L L SARCOMA OF B O N E
(Solitary when first seen.
CASE NO.
Ao~
Accepted as proven diagnosis by Bone Tumour Register. (6 eases)) SEx
II
5I
F.
144 18i 388 39° 397
42
F.
34 3
F. M.
56 71
F. M.
SITE
Femur Cervical spine Humerus Ear Ilium Clavicle
D.X.R. Dose 4000 r 2200 r 3200 r
46oo r IOOO r
3000 r
SURVIVAL TIME RECURRENCE
Treated with deep X rays
DEAD OR ALIVE
FREE
9 yr. 7 yr. 6 yr. 8 ruth. 7 mth. 7 mth.
Alive Alive Alive Dead (atypical case) Dead (secondaries in chest Dead (distant metastases)
RADIOSENSITIVE
BONE
TUMOURS
255
with colleagues who prefer to make no clear distinction between the types and label everything under the omnibus title ' Ewing ', then the only thing to do is to recognize that a proportion of all such Ewing's tumours may be curable and to treat all such solitary growths radically. We have treated secondary neuroblastoma with about the same dosage of" up to 3000 r, and have found that it is definitely less sensitive, and that in two-thirds of the cases only a little temporary relief was given. The cases of reticulosarcoma are listed in Table I. These are all the cases we have which were primary in bone, solitary when seen, and which were treated with deep X rays. Here, unless
Fig. 2 4 I . - - A case of reticulosarcoma of femur at the time of radiotherapy in 1945.
F~g, 242.--The same case as Fig. 24I nine years later. The extent of the abnormal bone is well shown.
the results are to be discarded as the results of chance in a small group, the record is much more hopeful. Half the cases have survived over six years and are apparently cured, and this agrees with the much larger American series. T h e level of dosage is again the same and ranges from 2000-4000 r. Case No. 388 is atypical" in two ways ; the patient was young (3 years), and the dose of 45oo r had only a slow and incomplete effect in making the tumour disappear. Two of the surviving cases are described below. Case I 4 4 . - - I n shoulders.
O c t o b e r , 1 9 4 7 , t h e p a t i e n t , a w o m a n a g e d 42, c o m p l a i n e d o f a s t a b b i n g p a i n b e t w e e n t h e In December a paralysis commenced and by April, 1948, she had an upper motor neurone paralysis
256
JOURNAL
OF
THE
FACULTY
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RADIOLOGISTS
at the level of D.V. 4, with incontinence of urine and sensation losses. A radiograph (Fig. 239) was thought to show an osteoelastoma but a biopsy of the spinous process of the vertebra showed reticulosarcoma. Treatment with 2200 r was given to the tumour in four weeks in April, 1948. By August there was return of sensation. In November, i948 , bladder control returned accompanied by spasms in the legs. In January, 1949, a tenotomy was performed to relieve the effects of the spasm of the adductors and hamstrings, after which the patient quickly began to walk. She is now walking well seven years later, and her general health is very good. A recent radiograph has shown the bodies of D.V. i and 2 to be fused (Fig. 240). Case i i . - - T h i s female patient was aged 51 years. In 1945 pain commenced in the right leg. rRadiographs showed a tumour of the femur (Fig. 24i ). Biopsy at first reported it to be a Ewing's tumour but scrutiny by the Bone T u m o u r Register gave a definite classification as reticulosarcoma. 4o0o r of deep X rays were given in two courses between September, 1945, and January, I946. Further radiographs in June, i946 , suggested that the lesion had completely healed. There have at no time been any signs of chest secondaries or of recurrence.
Fig. 243.--A tumour of the ilium, diagnosed as Ewing's tumour but probably reticulosarcoma, occurring in a girl of I5. A recent radiograph (Fig. 242) shows that the extent of bone repair is wider than the evidence of tumour in the first radiograph and shows the need to treat a wider field than will just cover the obvious tumour. T h e patient is very well now. T h i s case is a n i n e - y e a r survival and, as well as i l l u s t r a t i n g t h e possibilities of cure, s h o w s h o w s u c h a case t e n d s to h a v e a diagnosis o f E w i n g ' s t u m o u r f a s t e n e d o n to it u n l e s s it is well scrutinized. Lastly, t h e r e is o n e r e m a i n i n g case w h i c h c a m e to us l a b e l l e d E w i n g ' s t u m o u r , b u t u n f o r t u n ately t h e histological m a t e r i a l o n w h i c h t h i s d i a g n o s i s was b a s e d w a s n e v e r available to t h e Register, so this m a l i g n a n t t u r n o u t is n o t firmly classified. I t is, h o w e v e r , a n e x a m p l e of t h e fact t h a t w h e n ever a d i a g n o s i s of E w i n g ' s t u m o u r h a s n o t b e e n g i v e n b y e x p e r t o p i n i o n , k n o w n to h a v e e x c l u d e d o t h e r alternatives, t h e case m u s t be r e g a r d e d as c u r a b l e a n d radically t r e a t e d if possible.
Case 25.~-The patient was a girl of I5 when she came to us in January, 1942. She had had pain in the right hip for four months and was limping. On examination she had a firm mass in the right iliac fossa about I2 cm. in diameter. It was attached to the ilium and the swelling obscured the anterior superior spine. Biopsy had been performed in the Bristol Royal Infirmary one week previously and reported as Ewing's sarcoma. Blood-count and a chest radiograph were normal. T h e r a d i o g r a p h o f t h e pelvis is s h o w n i n Fig. 243, T h e r e is d e s t r u c t i o n of a m a j o r p a r t of t h e r i g h t i l i u m b y a n osteolytic t u m o u r . D e e p X - r a y t r e a t m e n t was s t a r t e d i n J a n u a r y , 1942.
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I5OO r were given in three weeks, widely to the whole area. The mass was very radiosensitive and by the end of treatment was much smaller. A radiograph four months later showed marked repair of the bone, and by April, 1946, bone repair was complete (Fig. 244). Another satisfactory point was that menstrual function had returned after the treatment, and in 1946 the patient was married, and though warned against pregnancy, was delivered in 1948 of
Fig. a 4 4 . - - T h e same t u m o u r as Fig. 243 four years after deep X - r a y treatment, normal pregnancy and delivery.
T h e patient t h e n married and went t h r o u g h She was well I3 years after treatment.
a 61-lb. normal child. A second child was born in 195o. She is still very well thirteen years after treatment. The X-ray dosage was on the low side, but fortunately the tumour was both very radiosensitive and radiocurable. The response to treatment and the long survival is much in favour of a diagnosis of reticulosarcoma.
MALIGNANT SYNOVIOMA We have in the Register only eight cases of this tumour (Table II). Of these patients, four survive at the present moment, but only two of them without recurrence. Both recurrence-free survivors received deep X-ray therapy. One of them is Case No. 176 on the list. The patient arrived with a diagnosis of synovioma already made as a result of a biopsy at the hospital of origin. The clinical evidence, site of tumour, metastases to inguinal glands, and the radiological appearances, were considered compatible with synovioma. Professor Hewer (1956) has reviewed the histology of the case and has accepted it as a clear example of the tumour. Deep X-ray therapy was given up to a high dose, 75oo r being given in nine weeks. At the end of this treatment a deep inguinal gland was found to be enlarged. The gland was excised by Professor Milnes Walker and 3ooo r deep X rays in 2I days were given to the groin. The patient has been very well for 6½ years now with no sign of recurrence since and uses her leg normally. The radiographs of this case appear in the paper by Dr. Ross (Ross, 1956) . The second case treated with deep X rays is a three-year survivor without recurrence. He also was given a high dose of deep X rays which was sufficient to cause radionecrosis, for which the leg had to be amputated.
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T h e third deep X-ray case was given a smaller dose of 35oo r, and here the tumour recurred after four years. T h e patient died with chest secondaries. Three of the cases were treated by local excision of the t u m o u r and have either died of the disease or now have recurrences. I n five cases the site of origin is adjacent to the lower end of the femur and this seems to be the site of election. Four of them had inguinal node metastases. This is only a small group so that one can only give very general indications of the best lines of treatment. One can see that this is indeed a very malignant t u m o u r with a pronounced tendency to Table/L--MALIGNANT SYNOVIOMA
(Cases with record of treatment (8 cases)) i
SITE OF TUMOUR
CASE AGE NO.
METHOD OF TREATMENT
DEAD OR
SURVIVAL TIME
RECURRENCE OR METASTASES
Recurrence locally aftra 3 yr. First local excision, thml glands in groin Secondaries in lung and scapula Chest, and glands in groin Chest, and glands in groin Glands of groin when first treated Nil Local recurrence in 4 yr.: then chest secondaries
ALIVE
421
29
Thumb
Local removal
Alive
3½ yr.
2IO
43
Near upper end of femur
Radical amputation
Dead
5½ yr.
457
58
Patella
Amputation
Dead
16 ruth.
640 63
Near lower end of femur
Local removal
Dead
I½ yr.
597
33
Near lower end of femur
Local removal
Alive
I½ yr.
~76
20
Near lower end of femur
D.X.R. 7500 r in 9 wk.
Alive
6½ yr.
426 89
50 32
Near lower end of femur Near lower end of femur
D.X.R. high dose D.X.R. 35oo r
Alive Dead
3 yr. 5 yr.
spread to both the lungs and the local lymph glands. Local excision is not a reliable treatment. T h e disease is clearly somewhat radiosensitive and responsive to irradiation, and can sometimes be cured by this m e a n s . . There may be an immediate reduction in size of both primary tumour and inguinal nodes, b u t a high dose is likely to be needed for the permanent destruction of the primary. As in the case of all bone tumours, high energy irradiation is the correct form of treatment to use and can be expected to give a greater margin of safety against necrosis than deep X rays when high doses are given. We in Bristol have had to use deep X rays up to the present time. Synovioma is more responsive than the general group of connective-tissue sarcomata, and irradiation should not be dismissed as a primary treatment. It is suggested that radiotherapy, preferably with high energy irradiation, may be used for the first radical attack on the tumour, and the only reliable alternative is amputation. A local excision must always be followe d by radical radiotherapy.
MYELOMATOSIS This is one of the commonest of bone tumours. It is a universally fatal tumour, and we are not in sight of any means of curing it. Treatment is therefore purely palliative. T h e main object in discussing so unpromising a disease is to give the results of the treatment of a few cases with radioactive phosphorus and to suggest that this is a good method of treatment useful in the majority of cases and occasionally producing great benefit. We have complete follow-up records of 47 cases of multiple myeloma to draw upon. I n addition, there are two of probably solitary myeloma. Seventeen of the 47 multiple cases have had treatment with pa2. T h e cases treated by different methods have been separated (Table III).
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T h e average t i m e of survival after pa2 is seen to be one year nine months. T h r e e of t h e cases in fact lived o v e r three years, and three over two years. G o o d relief of pain was o b t a i n e d in most of t h e m , and w e l l - b e i n g and activity were i m p r o v e d . T h e r e are nine cases w h i c h had t r e a t m e n t w i t h deep X rays to those parts of the skeleton w h i c h were p r o d u c i n g pain or other s y m p t o m s . T h e average survival here is only nine months. T h e Table IlL--MULTIPLE MYELOMA CASES
Method of Treatment p32 Deep X rays Surgical excision Stilbamidine None
No. of Cases 17 9 3 i 17
Average Survival Time I yr. 9 ruth. 9 mth. 4 ruth. 4 mth. 2½ mth.
cases were not selected and were similar in type and stage of a d v a n c e m e n t to those treated by p3~. T h e two longest survivals were each j u s t over two years. S e v e n t e e n cases had no t r e a t m e n t other t h a n s y m p t o m a t i c drugs not calculated to damage the t u m o u r . T h e average survival t i m e is only 21 months, b u t h e r e there has inevitably b e e n some selection, as the v e r y ill or dying patients were obviously less likely to be treated and this group is not c o m p a r a b l e w i t h the p32 group. M y o w n p r e s e n t feeling is that some f o r m of generalized t r e a t m e n t m u s t be given to attack this disease all over the b o d y and that, at present, pa~ is the best m e a n s of d o i n g this. It will usually produce a general relief of pain e v e r y w h e r e in the b o d y and significantly increases b o t h the total survival t i m e and, w h a t is also i m p o r t a n t , t h e w e l l - b e i n g and activity of the patient. D e e p X rays should, however, be also used in the same cases to deal f r o m t i m e to t i m e w i t h local r e c u r r e n c e of s y m p t o m s , since the total q u a n t i t y of pa~ used must, in the end, be limited by the tolerance of the bone marrow. T h e radiological appearances after pa~- t r e a t m e n t are, to s o m e extent, misleading, because v e r y little change is usually seen in the radiographs even w h e n relief of s y m p t o m s and i m p r o v e m e n t of activity is m o s t marked. T w o selected cases described b e l o w show the results sometimes obtainable. Case 7135.--A man aged 59 had had his disease nearly two years when, from the level of D.V. 2 and 3, complete paralysis occurred with incontinence of urine. Five mc. of p82 were given more or less as a despairing gesture and the patient sent to a chronic hospital. Two months later, movement of the toes re-appeared ; the improvement continued slowly and in August of that year 5 mc. of W 2 were given. By November, 1951, both legs were moving and his bedsores were healed. In April, I952--one year after the first dose--he was walking with crutches. Unfortunately he later developed heart failure and in April, I953, died with left ventricular failure and h~ematemesis. Case I i2o2.--This case, a woman aged 61, came to us in May, 1952. She was given a dose of 5 inc. of p82. Her white blood-count at that time was 64oo. She lost her pains and became more active. Repeat doses of p32 were given in March, 1953, and January, 1954, 8 inc. and 5 Inc. respectively. She has remained well for three years from then to the present time, except when she fell and hurt herself. Her white count in September, I954, was 3000. REFERENCES COLE'Z, B. L. (1949), Neoplasms of Bone and Related Conditions: Their Etiology, Pathogenesis, Diagnosis, and Treatment. New York : Hoeber. - - - - HIGINBOTHAM, N . L., and GROESBECK,H. P. (I954), Surg. Gynec. Obstet., 99, 142. EYRE-BRooK, A. L. (I956), J. Fan. Radiol., 7, 222. GESCHICKTER, C. F., and COPELAND, M. M. (I949) , Tumors of Bone, 3rd ed. Philadelphia and London: Lippincott. HEWER, T. F. (i956),J. Fac. Radiol., 7, 23o. LICHTENSTEIN, L . ( I 9 5 2 ) , Bone Tumours. London : Henry Kimpton. PARKE~, F., and JACKSON,H. (1939), Surg. Gynec. Obstet., 68, 45. Ross, F. G. M. (1956), ft. Fac. Radiol., 7, 242.