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Malignant diseases in children
MALIGNANT
DISEASES
IN CHILDREN*
M. B. BENNETT, D.M.R.
From Groote Schuur Hospital and Red Cross Children's Hospital, Cape Town, 1952-1961 IT must be noted that several difficulties confront one when dealing with malignant disease of childhood : - 1. Most people are not able to contemplate the subject of cancer in small children completely without emotion. I know that I am not. This tends to produce a refusal to recognise the problems involved at all. 2. Malignant diseases in children are not very common (for which let us be thankful). 3. The cases of malignant disease in children which do occur tend, in most centres of the world, to be scattered far and wide among the various specialties. Thus we see some go to the urologists, some to the ophthalmologists, some to the neurosurgeons, some to the general surgeons, some to the paediatricians and even some direct to the radiotherapists ! Thus any one doctor from among these specialists m a y only see a small group of children each year and no one of them builds UP good experience in dealing with children. We therefore feel that some one person, or group of people, should act as an integrating force amongst the specialties involved. It matters not whether that person b e surgeon or physician or radiotherapist as long as he or she is prepared to gather in all the available information on all childhood cases, register that information in some suitable way and follow what happens to each child, The "integrating " person does not need to treat personally every case--indeed he cannot. In Cape Town for the last ten years this has not been the case--although more or less inadvertently the radiotherapist has acted as " i n t e g r a t o r " to a certain extent. In future co-ordination and integration should improve since this year has seen the start of a weekly combined meeting to deal with children in our hospital, and so in the next ten years' time we hope to learn a great deal more than we have done in the past ten years. The Groote Schuur Hospital is the major teaching hospital in the Cape, being the teaching hospital for the University of Cape Town Medical School. Its radiotherapy department serves the whole of the Western Cape and South-West Africa and, to a lesser extent, cases come from the Eastern Cape.
Mainly, our cases come from the Western Province of the Cape, some from the more distant parts but about 60 per cent of the total from the immediate Cape Town locality. This total area of the Western Province of the Cape is inhabited by approximately two and a quarter million people composed of:--1,045,815 Cape Coloureds; 657,631 Whites; 503,780 Africans; and 12,779 Asiatics. O f this total some 787,712 live within the Cape Town area. For the local area we do know with some moderate degree of accuracy the composition of the population and the incidence of disease. In fact, for several years Professor J. M. Grieve has been conducting an intensive survey into the incidence of all types of malignant disease in this local area. These figures are not yet available, but it is possible to say that of about 4,000 patients with malignant disease registered in this local area in three years about eighty were children. This special unit also registered some fifty-five children who lived outside the local area but had been sent to Cape Town for treatment during the same period. This means that a special Children's T u m o u r Registry in Cape Town could expect to register at least forty-five cases per annum. These would be local and distant, hospital and private cases, and would include the acute leukaemias. As it is, I have to tell you of some 159 cases collected from the records of the radiotherapy department at Groote Schuur Hospital from 1952 to 1961. This total does not include the Ieukaemias. We feel, therefore, that it is important that we strive in future to collect all available information on the cases of cancer in children occurring in our area and we hope to be able to compare these with similarly collected figures from other parts of Africa. Here (Table 1) we should just note that ninetyseven non-white to sixty-two white children does not indicate an increased racial incidence as the 1960 census figures indicate that in our area there are more than twice as many colouredchildren under fifteen than there are white children. Our series of 159 children seen over ten years is indeed a fairly modest series when compared with some of the best known and quoted series of American and British figures, and we have chosen to fit our cases into a very simple grouping.
* Paper presented at the Central African Radiological Congress, Bulawayo, May, 1962 266
MALIGNANT
DISEASES
267
IN CHILDREN
TABLE 1
TABLE 2 T H E MISCELLANEOUS CASES
Total
Female
Non-
Male
white
I
Wilms's
31
15
!i 16
l
20
I
White 11
Neuroblastoma
26
13
! 13
i
8
18
Lymphoma
33
10
! 23
E
24
9
Cerebral
23
9
! 14
13
10
Retino
12
5
i
7
9
3
Miscellaneous
34
18
i
16
23
11
89
97
62
--
159
70
i
As we have explained, these figures represent cases coming from a very wide area and, apart from private patients, are probably fairly complete. It is known that there is no other hospital where radiotherapy can be obtained at present. It is of great interest to compare our figures with Manchester Children's Tumour Registry figures as this represents a very complete survey of a known area. They speak of only twenty-five Wilms's tumours out of 470 cases or very roughly 5 per cent (Campbell et al 1960). Dargeon (1960) speaks of ninety-three Wilms's tumours in a group of 1,418, i.e., roughly 6 per cent. In Kampala in a survey of 125 they have thirteen Wilms's or roughly 10 per cent, and D'Angio (1960) in Boston has twenty-six Wilms's in 250 cases or again 10 per cent. In our area Wilms's tumours seem to be the second commonest type of tumour, second only to lymphoma. Thus, while the average experience is of Wilms's tumour being 5 to 10 per cent of the total series, in our experience it represents nearly 20 per cent of the total. Another interesting point is that both the Manchester figures and the Dargeon figures show almost twice as many neuroblastomata as Wilms's tumours while we seem to have slightly larger numbers of Wilms's tumours. In this respect the Kampala series (Burkitt 1961 and O ' C o n o r 1960 and 1961) of 125 only shows three neuroblastomata. We have all been intrigued to read the work of the Kampala Group on lymphoma in African children and find the figure of 50 per cent of lymphoma rather staggering, most British and American figures seem to show l y m p h o m a as about 10 per cent or less of the total. Our own group seems to be in between with our roughly 20 per cent incidence of lymphoma and with a definite preponderance of non-European children. We have found that whereas in the Wilms's
Embryonal sarcoma Adrenal Liver Synovioma . Testicular Ovarian Unspecified retro-peritoneal Osteogenic sarcoma Thyroid Parotid Juvenile melanoma Fibro-sarcoma Sacro-coccygeal t u m o u r Squamous ca. jaw Sarcoma botryoides Eosinophil granuloma Myxo-sarcoma Anaplastic sarcoma Nasopharyngeal fibroma
I 1
3 2 2 2 1
4 3 1 1
1 1 1
2 4 1
2 1
34
tumour group the histological picture is usually characteristic and no doubt exists as to the diagnosis, we have had considerable difficulty in the other two groups and some cases in these groups have no very certain diagnosis but have been placed in the most likely group. In one instance a diagnosis of " most likely neuroblastoma " has given way to an autopsy report of reticulum-cell sarcoma and another " p r o b a b l e lymphosarcoma " on second biopsy proved to be " u n d o u b t e d l y neuroblastoma." So it seems we cannot speak of the divisions between the groups being particularly clear cut. I now want to look at some of our sub-groups in a little more detail. Let us take the Wilms's series first. We have only one known long-term survivor-a boy now aged twelve who was treated eleven years ago and therefore is not in this specific ten years. The first eight cases treated during 1951 to 1954 show little co-ordination of efforts of surgeon and radiotherapist. Of these, five are known to be dead and three are missing from follow-up (Table 3). F r o m 1954 to 1959 a further fifteen cases were treated. All these children underwent nephrectomy, all had D.X.R. (mainly given post-operatively and started on about the fourth or fifth post-operative day, but some had both pre- and post-operative D.X.R.).
268
CLINICAL TABLE 3
First Group--Eight cases
Five are dead. Three are missing. Second Group--Fifteen cases
Eleven are dead, all within eight months and all with lung metastasis or liver metastasis. One is missing. Three alive and well at five years, four years and three years. Third Group--Eight cases
Two who were both originally inoperable and had pre- and post-operative D.X.R. died within the usual eight months with lung metastasis. One died at fifteen months of kwashiorkor and at post-mortem showed no evidence of metastasis or recurrence. Five are alive at periods all well beyond eight months, i.e., at twenty-two months, twenty-three months, nineteen months, twenty-three months and sixteen months respectively, taken at end of April 1962.
The D.X.R. has in all cases been given through a pair of opposing fields to the affected loin. The zone from the diaphragm to the pelvic brim being irradiated. It has been our practice to include the whole width of the vertebral column in the hope that gross asymmetry of the vertebrae will not occur. Our one eleven-year survivor does however show some scoliosis and some deformity of the vertebrae within the irradiated area. Our dosage has varied from 2,500 r to 4,500 r delivered usually over a four, five or six week period. The majority of our patients having had 3,500 r over five weeks. Recommended dosage for this disease varies greatly and I do not feel that our dosage is inadequate. The third group (Table 3) appears to us to show a significant improvement, and we think this may be attributed to the addition of nitrogen mustard. The nitrogen mustard has been given on the basis of 0.1 mgm. per kilo body weight per day for four or five days. The first dose is given in the theatre at the time the surgeon commences to manipulate the tumour and the subsequent doses on the first, second and third post-operative days. The D.X.R. has sometimes been started as early as the third post-operative day, thus overlapping the chemotherapy and radiotherapy very slightly. There is, of course, no doubt that throughout the second and third groups of cases we have seen a steady improvement in the co-ordination of surgeon and radiotherapist in the management of these children, but this seems to date back to early 1954 rather than late 1959. The addition of nitrogen mustard as from the end of 1959 was the result of a review of the cases
RADIOLOGY
at that date. At that time two cases were missing from follow-up and we only knew of our one longterm survivor. Professor J. H. Louw and I were trying to see whether we were in any way providing inadequate treatment, and we found that the main point at which we differed from treatment given in other centres was that we did not start our D.X.R. until the fourth or fifth post-operative day. This gap we found impossible to close remembering that the children were operated on in one hospital, i.e., the Red Cross Memorial Hospital, and given their radiotherapy in another, i.e., Groote Schuur Hospital. It has always been our experience that the children are just not fit for radiotherapy until through the first three or fou r post-operative days. We felt then and still feel now that this gap of three, four or five days could be the vital factor, the presence of which leads to loss of nearly all the children with disseminate metastases in lungs and liver within eight months. This we thought might be combated by using some chemotherapeutic agent during and immediately after surgery. Nitrogen mustard was chosen as an agent with which we were familiar and which was relatively safe. We accepted a possible risk of delay in wound healing and possible severe haemopoietic depression, but this so far has not been met with. It may be of interest to note that Gross (1953) claims the prognosis to be much better in cases under twelve months. In our total series we only had one child under twelve months, the one case at six weeks of age. Eleven of our cases were under two years, seventeen between two and five years and four cases over five years of age. NEUROBLASTOMA Of our neuroblastoma cases it is extremely difficult to generalise. This is a disease producing such a diversity of lesions that it is difficult to produce two children whose lesions are in any way similar. Most people stress that this is one of the commonest neoplasms in children under four years of age. Some claim that more than half, indeed as many as 80 per cent (Reed 1928) are seen in children under two and a half years. This is not our experience. Four of our children were under one year, one child between one and two years, six children between two and five years and fourteen children over the age of five years. The majority of our cases, eighteen out of twenty-six, occurred in white children. In the vast majority of children palliative D.X.R., Mustine and Vitamin B12 have been the mainstay of treatment.
269
M A L I G N A N T DISEASES IN C H I L D R E N
Surgical removal of the primary lesion within the chest has twice been performed and partial surgical removal of neuroblastomatous mass by laminectomy once, but no removal of a primary adrenal tumour is recorded in this whole series. We have no long-term survivors in this series. We have noted no case of spontaneous regression and we have had no success with Vitamin B12. LYMPHOMA In this group of cases the non-white children predominate 24: 9 and males are more c o m m o n than females 23:10. The ages vary from ten months to fifteen years. In about a quarter of the cases the exact histology is uncertain, the diagnosis of an indefinite lymphoma or the possibility of neuroblastoma helping to create the impression that the division between these two groups of cases is not clear cut. In one case, for example, a biopsy diagnosis of lympho-epithelioma of the nasopharynx was changed at post-mortem examination, but only to an impossibility to say for certain whether the tumour was a reticulum-cell sarcoma or an extremely anaplastic squamous carcinoma. Children with lymphoma who have lived longer than one year are shown in Table 4. The Child illustrated (Figs. 1 and 2) is a case of
TABLE 4 1. 2. 3. 4. 5.
Hodgkin's para granuloma Hodgkin's disease Hodgkin's disease Hodgkin's disease Reticulum cell sarcoma of bone 6. Indefinite type lymphoma 7. ? lymphoma ? neuroblastoma
Alive without growth 7 years Alive with growth 6 years Alive with growth 1 year Alive with growth 1 year Died after 2½ years Alive without growth 7 years Alive without growth 2½ years
an indefinite type of lymphoma treated by D.X.R. in 1954 who remains well and free from disease eight years later. Attempting to sum up, I should like to say that malignant disease in childhood poses us many problems. There is the difficulty of giving the exact diagnostic label, which has been seen to be sometimes impossible. There is the difficulty that the natural history of many of these tumours seems so variable and the response to treatment often so unpredictable. There is the difficulty that so m a n y of our colleagues, and therefore most of the parents involved, hold such gloomy, pessimistic views about prognosis. Here in Africa there is the added difficulty that so many of the children show signs of varying degrees of malnutrition and thus seem to have less
FIG. 1 Fro. 2 FIG. l--Malignant lymphoma. FIG. 2--Lymphoma after treatment.
270
CLINICAL RADIOLOGY
h o s t resistance to the t u m o u r , a n d p o s s i b l y s h o w a less g o o d r a d i a t i o n r e s p o n s e for this r e a s o n . I t a p p e a r s to m e t h a t e v e r y effort s h o u l d be m a d e to g a t h e r all i n f o r m a t i o n t h a t is a v a i l a b l e to us a n d , i f possible, t o p o o l o u r i n f o r m a t i o n f r o m v a r i o u s A f r i c a n centres. W h i l e we d o n o t e x p e c t t h a t t h e f o r m a t i o n o f C h i l d r e n ' s T u m o u r Registries will c h a n g e t h e p i c t u r e o v e r n i g h t , we believe t h e y w o u l d d o m u c h to r e m o v e s o m e o f t h e c u r r e n t m i s c o n c e p t i o n s r e g a r d i n g t h i s g r o u p o f diseases. M e a n w h i l e , t h o s e o f us w h o see a n d t r e a t t h e s e c h i l d r e n m u s t s u m m o n all o u r e n e r g i e s to i m p r o v e t h e s t a n d a r d s o f surgical, r a d i o t h e r a p e u t i c a n d chemotherapeutic treatments, to improve the s t a n d a r d o f t e a m w o r k i n v o l v e d a n d to d o all this in a h o p e f u l , p o s i t i v e t h i n k i n g a n d c o m p a s s i o n a t e manner.
SUMMARY A s u r v e y is p r e s e n t e d o f m a l i g n a n t disease o c c u r r i n g in c h i l d r e n s e e n at G r o o t e S c h u u r H o s p i t a l and Red Cross Children's Hospital, Cape Town, f r o m 1952 to 1961. REFERENCES
ARIEL, I. M. & PACK, G. T. (1960).
Cancer and Allied Diseases of Infancy and Childhood. Boston: Little Brown. BURKITT, D. (1961). Cancer, 14, 258. CAMPBELL, A. C. P., GAISFORD, W., PATERSON, E. & STEWARD,J. K. (1961). Brit. reed. J. 1, 448. D'ANGIO (1960). Reports from Clinical Symposium. Texas Medical Centre, Nov. 1960. DARGEON,A. W. (1960). Tumours of Childhood. New York: Hoever. GRoss, R. (1953). The Surgery of Infancy and Childhood. Philadelphia: Saunders. O'CoNoR, G. T. (t961). Cancer, 14, 270. O'CONOR, G. T. (%DAVIES,J. N. P. (1960). J. Paediat. 56, 526.
BOOK REVIEW: continued from page 265 comments ate almost certainly influenced by the personal interest and prejudices of the reviewer. One of the radiotherapeutic techniques developed by the authors has been the treatment of malignant tumours by a Combination of external irradiation and a local implant. By this method, it is possible to raise the main tumour mass to a very high dose level, while taking the neighbouring tissues throughout a large volume to a lower dose which will be well tolerated. The technique has much to recommend it, and it is interesting to see in one publication so much data on this particular aspect of radiotherapy. At the first reading, the authors appeared to view overfavourably the techniques of irradiating with two opposed fields. When supervoltage therapy is used, this method is well tolerated in the early stages by the patient, but the late sequelae` may be exceedingly unpleasant, with severe subcutaneous and deep-tissue fibrosis. However, the authors are well aware of these dangers, and they suggest that, when using this technique, it may be advisable to use 22 MeV therapy rather than 6°Co. teletherapy, when subcutaneous fibrosis can be avoided. However, even this technique cannot spare deeper tissues, caught directly between the two fields at a depth of 4 cm. or more, and it would seem to be preferable to avoid the use of opposing fields as the only method of delivering an adequate turnout dose, unless this is the only technique which will ensure that the entire turnout is to be irradiated. Although it is very nice to be able to avoid over-irradiating the subcutaneous tissues, this is rarely dangerous, and serious after-effects are due to fibrosis of more deeply situated structures. In anycase, not manycentres will be in the fortunate position of possessing super-voltage units much above the 1 to 4 MeV level. Perhaps the authors might stress, even more, the limitations of two opposing fields in the inevitable next edition of this delightful book. The reviewer agrees wholeheartedly with the authors' views on the limitations of palliative radiotherapy in this region. As a general rule, the required dose approximates very closely to that which is usually regarded as necessary for attempted cure. The authors' views on such controversial subjects as dental care, bone necrosis after supervoltage irradiation and the management of necrosis are stated with remarkable
clarity, and argued with reasonable logic. All workers in this field will not necessarily agree with these views but it is extremely difficult to argue against them with our present extremely limited factual knowledge. Useful appendices are included on the use of the life table method of survival analysis, and on various basic aspects of implantation dosage. The book is lavishly illustrated-many of the 119 figures include " A," " B " and " c " - - b u t the illustrations are never superfluous. The reader has the usual feeling that the implant radiographs are " t o o good to be true," but it is only natural for the authors to select radiographs which show what can be done in highly skilled hands, and not what may occasionally occur. It would be refreshing to read a publication wherein is stated the percentage of implants that approximated to the ideal, and how many gave a marked variation in dose throughout the volume. Such a publication would be extraordinarily heartening to mere mortals such as the reviewer. This is a minor criticism by a reviewer who is struggling hard to find some adverse criticism to balance up the lavish Praise that he feels should be given. Not only are the radiographs excellent, but the text is interspersed with first-class line drawings, which help greatly in its understanding. Each illustration is apt and none is repetitive. A possible misprint occurs on page 41, where the authors refer to the use of implants delivering doses of 7,000 to 7,500 r for small volumes, and 10,000 to 14,000 for large volttmes. This is the only possible error that the reviewer was able to discover. The whole volume is clearly set out, and beautifully produced, as behoves a Thomas publication--except of course, for the usual extremely irritating publisher's comments on the inside of the paper cover. In brief, this is a completely outstanding book, which is unique in its class. It gives the reviewer the greatest possible pleasure to congratulate the senior authors and their collaborators on such a first-class volume, which must inevitably become the standard reference work on the management of cancer arising in this region. It is to be hoped that they are working hard at the next edition, which will be demanded widely in the very near future. A. M. JELLIFFE.
DISEASES
IN CHILDREN*
M. B. BENNETT, D.M.R.
From Groote Schuur Hospital and Red Cross Children's Hospital, Cape Town, 1952-1961 IT must be noted that several difficulties confront one when dealing with malignant disease of childhood : - 1. Most people are not able to contemplate the subject of cancer in small children completely without emotion. I know that I am not. This tends to produce a refusal to recognise the problems involved at all. 2. Malignant diseases in children are not very common (for which let us be thankful). 3. The cases of malignant disease in children which do occur tend, in most centres of the world, to be scattered far and wide among the various specialties. Thus we see some go to the urologists, some to the ophthalmologists, some to the neurosurgeons, some to the general surgeons, some to the paediatricians and even some direct to the radiotherapists ! Thus any one doctor from among these specialists m a y only see a small group of children each year and no one of them builds UP good experience in dealing with children. We therefore feel that some one person, or group of people, should act as an integrating force amongst the specialties involved. It matters not whether that person b e surgeon or physician or radiotherapist as long as he or she is prepared to gather in all the available information on all childhood cases, register that information in some suitable way and follow what happens to each child, The "integrating " person does not need to treat personally every case--indeed he cannot. In Cape Town for the last ten years this has not been the case--although more or less inadvertently the radiotherapist has acted as " i n t e g r a t o r " to a certain extent. In future co-ordination and integration should improve since this year has seen the start of a weekly combined meeting to deal with children in our hospital, and so in the next ten years' time we hope to learn a great deal more than we have done in the past ten years. The Groote Schuur Hospital is the major teaching hospital in the Cape, being the teaching hospital for the University of Cape Town Medical School. Its radiotherapy department serves the whole of the Western Cape and South-West Africa and, to a lesser extent, cases come from the Eastern Cape.
Mainly, our cases come from the Western Province of the Cape, some from the more distant parts but about 60 per cent of the total from the immediate Cape Town locality. This total area of the Western Province of the Cape is inhabited by approximately two and a quarter million people composed of:--1,045,815 Cape Coloureds; 657,631 Whites; 503,780 Africans; and 12,779 Asiatics. O f this total some 787,712 live within the Cape Town area. For the local area we do know with some moderate degree of accuracy the composition of the population and the incidence of disease. In fact, for several years Professor J. M. Grieve has been conducting an intensive survey into the incidence of all types of malignant disease in this local area. These figures are not yet available, but it is possible to say that of about 4,000 patients with malignant disease registered in this local area in three years about eighty were children. This special unit also registered some fifty-five children who lived outside the local area but had been sent to Cape Town for treatment during the same period. This means that a special Children's T u m o u r Registry in Cape Town could expect to register at least forty-five cases per annum. These would be local and distant, hospital and private cases, and would include the acute leukaemias. As it is, I have to tell you of some 159 cases collected from the records of the radiotherapy department at Groote Schuur Hospital from 1952 to 1961. This total does not include the Ieukaemias. We feel, therefore, that it is important that we strive in future to collect all available information on the cases of cancer in children occurring in our area and we hope to be able to compare these with similarly collected figures from other parts of Africa. Here (Table 1) we should just note that ninetyseven non-white to sixty-two white children does not indicate an increased racial incidence as the 1960 census figures indicate that in our area there are more than twice as many colouredchildren under fifteen than there are white children. Our series of 159 children seen over ten years is indeed a fairly modest series when compared with some of the best known and quoted series of American and British figures, and we have chosen to fit our cases into a very simple grouping.
* Paper presented at the Central African Radiological Congress, Bulawayo, May, 1962 266
MALIGNANT
DISEASES
267
IN CHILDREN
TABLE 1
TABLE 2 T H E MISCELLANEOUS CASES
Total
Female
Non-
Male
white
I
Wilms's
31
15
!i 16
l
20
I
White 11
Neuroblastoma
26
13
! 13
i
8
18
Lymphoma
33
10
! 23
E
24
9
Cerebral
23
9
! 14
13
10
Retino
12
5
i
7
9
3
Miscellaneous
34
18
i
16
23
11
89
97
62
--
159
70
i
As we have explained, these figures represent cases coming from a very wide area and, apart from private patients, are probably fairly complete. It is known that there is no other hospital where radiotherapy can be obtained at present. It is of great interest to compare our figures with Manchester Children's Tumour Registry figures as this represents a very complete survey of a known area. They speak of only twenty-five Wilms's tumours out of 470 cases or very roughly 5 per cent (Campbell et al 1960). Dargeon (1960) speaks of ninety-three Wilms's tumours in a group of 1,418, i.e., roughly 6 per cent. In Kampala in a survey of 125 they have thirteen Wilms's or roughly 10 per cent, and D'Angio (1960) in Boston has twenty-six Wilms's in 250 cases or again 10 per cent. In our area Wilms's tumours seem to be the second commonest type of tumour, second only to lymphoma. Thus, while the average experience is of Wilms's tumour being 5 to 10 per cent of the total series, in our experience it represents nearly 20 per cent of the total. Another interesting point is that both the Manchester figures and the Dargeon figures show almost twice as many neuroblastomata as Wilms's tumours while we seem to have slightly larger numbers of Wilms's tumours. In this respect the Kampala series (Burkitt 1961 and O ' C o n o r 1960 and 1961) of 125 only shows three neuroblastomata. We have all been intrigued to read the work of the Kampala Group on lymphoma in African children and find the figure of 50 per cent of lymphoma rather staggering, most British and American figures seem to show l y m p h o m a as about 10 per cent or less of the total. Our own group seems to be in between with our roughly 20 per cent incidence of lymphoma and with a definite preponderance of non-European children. We have found that whereas in the Wilms's
Embryonal sarcoma Adrenal Liver Synovioma . Testicular Ovarian Unspecified retro-peritoneal Osteogenic sarcoma Thyroid Parotid Juvenile melanoma Fibro-sarcoma Sacro-coccygeal t u m o u r Squamous ca. jaw Sarcoma botryoides Eosinophil granuloma Myxo-sarcoma Anaplastic sarcoma Nasopharyngeal fibroma
I 1
3 2 2 2 1
4 3 1 1
1 1 1
2 4 1
2 1
34
tumour group the histological picture is usually characteristic and no doubt exists as to the diagnosis, we have had considerable difficulty in the other two groups and some cases in these groups have no very certain diagnosis but have been placed in the most likely group. In one instance a diagnosis of " most likely neuroblastoma " has given way to an autopsy report of reticulum-cell sarcoma and another " p r o b a b l e lymphosarcoma " on second biopsy proved to be " u n d o u b t e d l y neuroblastoma." So it seems we cannot speak of the divisions between the groups being particularly clear cut. I now want to look at some of our sub-groups in a little more detail. Let us take the Wilms's series first. We have only one known long-term survivor-a boy now aged twelve who was treated eleven years ago and therefore is not in this specific ten years. The first eight cases treated during 1951 to 1954 show little co-ordination of efforts of surgeon and radiotherapist. Of these, five are known to be dead and three are missing from follow-up (Table 3). F r o m 1954 to 1959 a further fifteen cases were treated. All these children underwent nephrectomy, all had D.X.R. (mainly given post-operatively and started on about the fourth or fifth post-operative day, but some had both pre- and post-operative D.X.R.).
268
CLINICAL TABLE 3
First Group--Eight cases
Five are dead. Three are missing. Second Group--Fifteen cases
Eleven are dead, all within eight months and all with lung metastasis or liver metastasis. One is missing. Three alive and well at five years, four years and three years. Third Group--Eight cases
Two who were both originally inoperable and had pre- and post-operative D.X.R. died within the usual eight months with lung metastasis. One died at fifteen months of kwashiorkor and at post-mortem showed no evidence of metastasis or recurrence. Five are alive at periods all well beyond eight months, i.e., at twenty-two months, twenty-three months, nineteen months, twenty-three months and sixteen months respectively, taken at end of April 1962.
The D.X.R. has in all cases been given through a pair of opposing fields to the affected loin. The zone from the diaphragm to the pelvic brim being irradiated. It has been our practice to include the whole width of the vertebral column in the hope that gross asymmetry of the vertebrae will not occur. Our one eleven-year survivor does however show some scoliosis and some deformity of the vertebrae within the irradiated area. Our dosage has varied from 2,500 r to 4,500 r delivered usually over a four, five or six week period. The majority of our patients having had 3,500 r over five weeks. Recommended dosage for this disease varies greatly and I do not feel that our dosage is inadequate. The third group (Table 3) appears to us to show a significant improvement, and we think this may be attributed to the addition of nitrogen mustard. The nitrogen mustard has been given on the basis of 0.1 mgm. per kilo body weight per day for four or five days. The first dose is given in the theatre at the time the surgeon commences to manipulate the tumour and the subsequent doses on the first, second and third post-operative days. The D.X.R. has sometimes been started as early as the third post-operative day, thus overlapping the chemotherapy and radiotherapy very slightly. There is, of course, no doubt that throughout the second and third groups of cases we have seen a steady improvement in the co-ordination of surgeon and radiotherapist in the management of these children, but this seems to date back to early 1954 rather than late 1959. The addition of nitrogen mustard as from the end of 1959 was the result of a review of the cases
RADIOLOGY
at that date. At that time two cases were missing from follow-up and we only knew of our one longterm survivor. Professor J. H. Louw and I were trying to see whether we were in any way providing inadequate treatment, and we found that the main point at which we differed from treatment given in other centres was that we did not start our D.X.R. until the fourth or fifth post-operative day. This gap we found impossible to close remembering that the children were operated on in one hospital, i.e., the Red Cross Memorial Hospital, and given their radiotherapy in another, i.e., Groote Schuur Hospital. It has always been our experience that the children are just not fit for radiotherapy until through the first three or fou r post-operative days. We felt then and still feel now that this gap of three, four or five days could be the vital factor, the presence of which leads to loss of nearly all the children with disseminate metastases in lungs and liver within eight months. This we thought might be combated by using some chemotherapeutic agent during and immediately after surgery. Nitrogen mustard was chosen as an agent with which we were familiar and which was relatively safe. We accepted a possible risk of delay in wound healing and possible severe haemopoietic depression, but this so far has not been met with. It may be of interest to note that Gross (1953) claims the prognosis to be much better in cases under twelve months. In our total series we only had one child under twelve months, the one case at six weeks of age. Eleven of our cases were under two years, seventeen between two and five years and four cases over five years of age. NEUROBLASTOMA Of our neuroblastoma cases it is extremely difficult to generalise. This is a disease producing such a diversity of lesions that it is difficult to produce two children whose lesions are in any way similar. Most people stress that this is one of the commonest neoplasms in children under four years of age. Some claim that more than half, indeed as many as 80 per cent (Reed 1928) are seen in children under two and a half years. This is not our experience. Four of our children were under one year, one child between one and two years, six children between two and five years and fourteen children over the age of five years. The majority of our cases, eighteen out of twenty-six, occurred in white children. In the vast majority of children palliative D.X.R., Mustine and Vitamin B12 have been the mainstay of treatment.
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Surgical removal of the primary lesion within the chest has twice been performed and partial surgical removal of neuroblastomatous mass by laminectomy once, but no removal of a primary adrenal tumour is recorded in this whole series. We have no long-term survivors in this series. We have noted no case of spontaneous regression and we have had no success with Vitamin B12. LYMPHOMA In this group of cases the non-white children predominate 24: 9 and males are more c o m m o n than females 23:10. The ages vary from ten months to fifteen years. In about a quarter of the cases the exact histology is uncertain, the diagnosis of an indefinite lymphoma or the possibility of neuroblastoma helping to create the impression that the division between these two groups of cases is not clear cut. In one case, for example, a biopsy diagnosis of lympho-epithelioma of the nasopharynx was changed at post-mortem examination, but only to an impossibility to say for certain whether the tumour was a reticulum-cell sarcoma or an extremely anaplastic squamous carcinoma. Children with lymphoma who have lived longer than one year are shown in Table 4. The Child illustrated (Figs. 1 and 2) is a case of
TABLE 4 1. 2. 3. 4. 5.
Hodgkin's para granuloma Hodgkin's disease Hodgkin's disease Hodgkin's disease Reticulum cell sarcoma of bone 6. Indefinite type lymphoma 7. ? lymphoma ? neuroblastoma
Alive without growth 7 years Alive with growth 6 years Alive with growth 1 year Alive with growth 1 year Died after 2½ years Alive without growth 7 years Alive without growth 2½ years
an indefinite type of lymphoma treated by D.X.R. in 1954 who remains well and free from disease eight years later. Attempting to sum up, I should like to say that malignant disease in childhood poses us many problems. There is the difficulty of giving the exact diagnostic label, which has been seen to be sometimes impossible. There is the difficulty that the natural history of many of these tumours seems so variable and the response to treatment often so unpredictable. There is the difficulty that so m a n y of our colleagues, and therefore most of the parents involved, hold such gloomy, pessimistic views about prognosis. Here in Africa there is the added difficulty that so many of the children show signs of varying degrees of malnutrition and thus seem to have less
FIG. 1 Fro. 2 FIG. l--Malignant lymphoma. FIG. 2--Lymphoma after treatment.
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h o s t resistance to the t u m o u r , a n d p o s s i b l y s h o w a less g o o d r a d i a t i o n r e s p o n s e for this r e a s o n . I t a p p e a r s to m e t h a t e v e r y effort s h o u l d be m a d e to g a t h e r all i n f o r m a t i o n t h a t is a v a i l a b l e to us a n d , i f possible, t o p o o l o u r i n f o r m a t i o n f r o m v a r i o u s A f r i c a n centres. W h i l e we d o n o t e x p e c t t h a t t h e f o r m a t i o n o f C h i l d r e n ' s T u m o u r Registries will c h a n g e t h e p i c t u r e o v e r n i g h t , we believe t h e y w o u l d d o m u c h to r e m o v e s o m e o f t h e c u r r e n t m i s c o n c e p t i o n s r e g a r d i n g t h i s g r o u p o f diseases. M e a n w h i l e , t h o s e o f us w h o see a n d t r e a t t h e s e c h i l d r e n m u s t s u m m o n all o u r e n e r g i e s to i m p r o v e t h e s t a n d a r d s o f surgical, r a d i o t h e r a p e u t i c a n d chemotherapeutic treatments, to improve the s t a n d a r d o f t e a m w o r k i n v o l v e d a n d to d o all this in a h o p e f u l , p o s i t i v e t h i n k i n g a n d c o m p a s s i o n a t e manner.
SUMMARY A s u r v e y is p r e s e n t e d o f m a l i g n a n t disease o c c u r r i n g in c h i l d r e n s e e n at G r o o t e S c h u u r H o s p i t a l and Red Cross Children's Hospital, Cape Town, f r o m 1952 to 1961. REFERENCES
ARIEL, I. M. & PACK, G. T. (1960).
Cancer and Allied Diseases of Infancy and Childhood. Boston: Little Brown. BURKITT, D. (1961). Cancer, 14, 258. CAMPBELL, A. C. P., GAISFORD, W., PATERSON, E. & STEWARD,J. K. (1961). Brit. reed. J. 1, 448. D'ANGIO (1960). Reports from Clinical Symposium. Texas Medical Centre, Nov. 1960. DARGEON,A. W. (1960). Tumours of Childhood. New York: Hoever. GRoss, R. (1953). The Surgery of Infancy and Childhood. Philadelphia: Saunders. O'CoNoR, G. T. (t961). Cancer, 14, 270. O'CONOR, G. T. (%DAVIES,J. N. P. (1960). J. Paediat. 56, 526.
BOOK REVIEW: continued from page 265 comments ate almost certainly influenced by the personal interest and prejudices of the reviewer. One of the radiotherapeutic techniques developed by the authors has been the treatment of malignant tumours by a Combination of external irradiation and a local implant. By this method, it is possible to raise the main tumour mass to a very high dose level, while taking the neighbouring tissues throughout a large volume to a lower dose which will be well tolerated. The technique has much to recommend it, and it is interesting to see in one publication so much data on this particular aspect of radiotherapy. At the first reading, the authors appeared to view overfavourably the techniques of irradiating with two opposed fields. When supervoltage therapy is used, this method is well tolerated in the early stages by the patient, but the late sequelae` may be exceedingly unpleasant, with severe subcutaneous and deep-tissue fibrosis. However, the authors are well aware of these dangers, and they suggest that, when using this technique, it may be advisable to use 22 MeV therapy rather than 6°Co. teletherapy, when subcutaneous fibrosis can be avoided. However, even this technique cannot spare deeper tissues, caught directly between the two fields at a depth of 4 cm. or more, and it would seem to be preferable to avoid the use of opposing fields as the only method of delivering an adequate turnout dose, unless this is the only technique which will ensure that the entire turnout is to be irradiated. Although it is very nice to be able to avoid over-irradiating the subcutaneous tissues, this is rarely dangerous, and serious after-effects are due to fibrosis of more deeply situated structures. In anycase, not manycentres will be in the fortunate position of possessing super-voltage units much above the 1 to 4 MeV level. Perhaps the authors might stress, even more, the limitations of two opposing fields in the inevitable next edition of this delightful book. The reviewer agrees wholeheartedly with the authors' views on the limitations of palliative radiotherapy in this region. As a general rule, the required dose approximates very closely to that which is usually regarded as necessary for attempted cure. The authors' views on such controversial subjects as dental care, bone necrosis after supervoltage irradiation and the management of necrosis are stated with remarkable
clarity, and argued with reasonable logic. All workers in this field will not necessarily agree with these views but it is extremely difficult to argue against them with our present extremely limited factual knowledge. Useful appendices are included on the use of the life table method of survival analysis, and on various basic aspects of implantation dosage. The book is lavishly illustrated-many of the 119 figures include " A," " B " and " c " - - b u t the illustrations are never superfluous. The reader has the usual feeling that the implant radiographs are " t o o good to be true," but it is only natural for the authors to select radiographs which show what can be done in highly skilled hands, and not what may occasionally occur. It would be refreshing to read a publication wherein is stated the percentage of implants that approximated to the ideal, and how many gave a marked variation in dose throughout the volume. Such a publication would be extraordinarily heartening to mere mortals such as the reviewer. This is a minor criticism by a reviewer who is struggling hard to find some adverse criticism to balance up the lavish Praise that he feels should be given. Not only are the radiographs excellent, but the text is interspersed with first-class line drawings, which help greatly in its understanding. Each illustration is apt and none is repetitive. A possible misprint occurs on page 41, where the authors refer to the use of implants delivering doses of 7,000 to 7,500 r for small volumes, and 10,000 to 14,000 for large volttmes. This is the only possible error that the reviewer was able to discover. The whole volume is clearly set out, and beautifully produced, as behoves a Thomas publication--except of course, for the usual extremely irritating publisher's comments on the inside of the paper cover. In brief, this is a completely outstanding book, which is unique in its class. It gives the reviewer the greatest possible pleasure to congratulate the senior authors and their collaborators on such a first-class volume, which must inevitably become the standard reference work on the management of cancer arising in this region. It is to be hoped that they are working hard at the next edition, which will be demanded widely in the very near future. A. M. JELLIFFE.