Th:s report is based essentially on 45 patients with Wilms' tumour treated during  the period 1951 - 1967 with comments on a modified regime in 20 patients treaed  since 1968. During the period 1951 - 1967 the standard treatment was  nephrec:omy and radiotherapy; cy:oxics were added from 1959. The overall   long-term survival was 42%, but all infants under the age of 1 Year have survived.  Cytoxics increased the  over-all survival rate from 19% to 55%. Although we aimed at giving pos~operative  irradiation only, 10 patients received pre-operarve therapy because of the enormous size of their tumours and/or malnu:rit1on. Eight of these patients have survived. In view of the above, all patients, excepting infants under 1 year, have received pre- and  postoperative X-ray therapy since 1968. We have also modified the cytoxic regime and all patien~s have been given repeated courses of actinomycin 0, while those with  metastases or recurrence have also received vincristine. The over-all survival rate to date [s 60%

Louw, J.H.

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J. H. LOUW, CH.M., F.R.C.S., Professor of Surgery, University of Cape TownThe Management of Wilms' Tumour *S.-A. MEDIESE TYDSKRIF 1065SURGERYRadiotherapy is also I egarded as essential by mostworkers, although there is now a strong body of opinion infavour of withholding radiotherapy in infants under theage of 1 year and it has been proposed that radiotherapy-can be omitted in Stage I tumours in older children. Bethat as it may, we have used radiotherapy in a total dosageof up to 3000 rads (depending on age) spread over 3 - 4weeks, whenever possible. In most of the 45 patients it wasgiven postoperatively only. commencing 3 - 4 days afterthe operation.The value of pre-operative irradiation remains a contro-versial issue and there are many who condemn it outright.This used to be our viewpoint but because of the largesize and fixity of some tumours and the poor nutrition-al state of many of our patients, we have been forced toresort to pre-operative therapy (up to a dose of 1 200 rads)in about 25 % of cases. The results have been most signifi-cant, especially when correlated with the ages of thepatients (Table I). With the use of pre-operative radio-therapy the over-all long-term survival was 80 % as com-pared with 31 o~ when only postoperative irradiation wasgiven. This was indeed a surprising finding because thechildren who received pre-operative irradiation werepoorer risks, with larger tumours. It should also be notedthat the improved results were obtained in children overthe age of I year. There is little doubt that in the type ofpatient seen by us and in our hands, pre-operative therapyhas improved the results in children over the age of 12months and particularly in those over 3 years. It certainlyrenders the surgery much easier and lessens the risks oflocal recurrence and of rupture of the tumour duringmanipulation. Since 1968 we have, therefore, used pre-operative radiotherapy in all children over 1 year old.It ras to be conceded that this method of treatment de-mands absolute accuracy of diagnosis and for this reasonwe have had to perform arteriography in many of theRADIOTHERAPYSurgery is essential, although there are records of a fewcases with bilateral tumours who have survived withoutremoval of the second kidney. The operation which aimsat early ligation of the pedicle and dissection of the neigh-bouring glands, is best performed by the transperitonealapproach. This is particularly important when there hasbeen extension into the inferior vena cava. Surgery alsoplays a role in the treatment of isolated secondaries, e.g.solitary pulmonary metastases, afl.d one of our patients inwhom such a metastasis was excised is still alive and well4 years later.SUMMARYTh:s report is based essentially on 45 patients with Wilms'tumour treated during the period 1951 - 1967 with com-ments on a modified regime in 20 patients trea~ed since1968.During the period 1951 - 1967 the standard treatmentwas nephrec:omy and radiotherapy; cy:oxics were addedfrom 1959. The over-all long-term survival was 42%, butall infants under the age of 1 Year have survived. Cy-toxics increased the over-all survival rate from 19% to55%. Although we aimed at giving pos~operative irradiationonly, 10 patients received pre-operarve therapy becauseof the enormous size of their tumours and/or malnu:rit1on.Eight of these patients have survived.In view of the above, all patients, excepting infantsunder 1 year, have received pre- and postoperative X-raytherapy since 1968. We have also modified the cytoxicregime and all patien~s have been given repeated coursesof actinomycin 0, while those with metastases or recur-rence have also received vincristine. The over-all survivalrate to date [s 60%.S. Afr. Med. l., 45, 1065 (1971).~Paper pre"ented at the 8th Congress of the Urological Association ofSouth Africa (M.A.S.A.), held in 'Cape Town on 1 - 5 February 1971In the period 1951 - 1970 the Childhood Tumour Clinicof the University of Cape Town dealt with 808 cases ofmalignant disease in childhood. Of these patients, 79children (9'7~o) suffen:d from Wilms' tumours which formthe basis of this discussion.In the management of Wilms' tumours, as indeed in thatof any childhood neoplasm, the first step is to ensureminimal handling of the tumour to avoid unnecessarydislodgement of malignant cells into the circulation. Specialinvestigations should be restricted and in most caseslimited to X-ray of the chest, intravenous pyelographyand possibly arteriography.The standard treatment for Wilms' tumour today con-sists of a combination of surgery, radiotherapy and c~emo­therapy, although in infants ufl.der the age of I year, oneor both of the latter modalities may be omitted. Of the79 cases in our series 14 arrived in a terminal state due tometastases, malnutrition or intercurrent disease. They diedwithin a few days of admission and will not be considered.Twenty have been treated since 1967 and because thefollow-up is less than 3 years these cases are not in~ludedin the detailed analysis of the results of treatment. Thisarticle, therefore, deals essentially with the methods andresults of treatment in 45 cases adequately treated duringthe period 1951 - 1967. However, since 1968 we havemodified our treatment and therefore a few remarks onthe methods used and results obtained in the last 20 casesmay be of interest.2 Okiob~r 19711066 S.A. MEDICAL JOURNAL 2 October 1971TABLE I. RADIOTHERAPYPostoperative DXR only Pre- and postoperative DXRNo. of cases Survivors Survival rate No. of cases Survivors Survival rateLess than 1 year 2 2 100% 1 1 100%12 - 35 months 17 7 41% 3 3 100%More than 3 years 16 2 13% 6 4 67%Totals 35 11 31% 10 8 80%CYTOTOXICSlating the results with the stage of the tumours. Table IIIshows that there has been an improvement in all stages,but particularly in the more advanced cases.Cytotoxics have now become almost a sine qua non inthe treatment of Wilms' tumour. We have used cytotoxicssince 1959-nitrogen mustard from 1959 to 1962 andactinomycin D from 1963 to 1967-with considerable im-provement in our overall results-from 19% to 55 % (TableII). The effect of cytotoxics is better illustrated by corre-patients. The arteriograms have proved to be of inestimablevalue, not only in confirming the diagnosis, but also inexcluding the presence of a second tumour in the otherkidney.Radiotherapy is also of some value in the treatment ofmultiple pulmonary metastases and we have used it in adosage of I 250 rads with favourable, although temporary,results.In recent times long-term cytotoxic therapy given inrepeated courses has been favoured by most workers andactinomycin D in a dosage of 75 p.g/ kg/ course has re-mained the most popular drug. This used to be given individed doses of 15 p.g / kg /day on 5 successive days, butwe have found that in undernourished children the dailydose often had alarming toxic effects. We have, therefore,changed to a divided dosage of 10 p.g/kg/day on 8 succes-sive days. Many workers have also been favourably im-pressed by vincristine and are using it either as an alterna-tive to actinomycin D or, more frequently, in addition toactinomycin D.Since 1968 we have, therefore, employed the followingregime:1. Actinomycin D intra- and peri-operativeIy in a dosageof 10 p.g/kg on 8 successive days starting intra-operatively in those who have immediate nephrecto-mies and I day pre-operatively in those who havepre·operative DXR.2. This is followed by repeated courses of actinomycinD 10 p.g/kg on 8 successive days after 6 weeks andthen every 2 - 3 months depending on the bloodcount for a total period of 12 - 18 months.3. In patients with recurrence or metastases, vincristine0·05 mg/kg intravenously is given at weekly intervalsin the periods between actinomycin D therapy.It is still too early to assess the results of this regimesince the children have been only followed up for 3months to 3 years. Suffice it to say that at present 12 of the20 children (i.e. 6000) are alive and well and that there hasbeen quite remarkable regression of metastases in anumber of cases.19%56%55%Survival rate3511No. of Ciises SurvivorsTABLE 11. CYTOTOXIC THERAPYCytotoxicsNil (1951 - 58) 16Mustine (1959 - 62) 9Actinomycin D (1963 - 67) 20TABLE Ill. EFFECT OF CYTOTOXIC THERAPY ON VARIOUS STAGES1951 - 58: No cytotoxics 1959 - 67: Cyt.otoxicsStage No. of cases Survivors Survival rate No. of cases Survivors Survival rateI 6 2 33% 13 10 77%11 4 1 25% 7 4 57%III 2 0 0 8 2 25%IV 3 0 0 1 0 0V 1 0 0Totals 16 3 19% 29 16 56%-2 Oktober 1971 S.-A. MEDIESE TVDSKRIF 1067SURVIVAL RATESOur over-all survival rates during the period 1951 - 1967,viz. 42 % for all cases treated and 56 % for those in whomcytotoxics were used, do not measure up to figures quotedfrom the USA and UK. There are three possible reasonsfor this:for major surgery, contributed to poor wound healing andmade postoperative radiotherapy necessary in many cases.Moreover, malnutrition contributed to at least 6 of thelater deaths and in 2 of them autopsy revealed no evidenceof tumour!TABLE V. EFFECT OF STAGE ON PROGNOSISOur present treatment regime may be summarized asfollows:1. Pre-operative DXR to 1 200 rads.2. Nephrectomy covered by actinomycin D 10 JJ.g/ kgon 8 successive days.3. Postoperative DXR 750 - 1 000 rads/week up to atotal dose (including the pre-operative dose) as follows:Under I year-2000 rads;; to 1t years-2 500 rads;It years and over-3 000 rads.4. Repeated courses of actinomycin D at 6 - 8-week inter-vals for 12 - 18 mon ths.5. Single metastases: surgical excision covered by actino-mycin D, followed by alternating courses of actinomycin D(as above) and vincristine 0·05 mg/ kg at weekly intervalsduring the intervening period.6. Multiple metastases: DXR up to 1 250 rads coveredby actinomycin D and followed by alternating courses ofactinomycin D and vincristine.This paper is based on the work of the Childhood TumourClinic of the University of Cape Town and is a preliminaryreport on only a small aspect of the work which will bereported in greater detail in the near future. The patients weretreated at the Red Cross War Memorial Children's Hospitaland Groote Schuur Hospital, Cape Town. As Chairman of theChildhood Tumour Clinic, I wish to express my indebtednessto all members of the Clinic for their various contributions. Ialso wish to thank the surgeons, radiologists, pathologists andothers who have been responsible for the care of the patientsat the respective hospitals. My thanks are also due to theSuperintendents of the Hospitals for permission to publish thedata.PRESENT POLICY OF TREATMENTTotals 45I 711 5III 4IV 3V 1Totals 20The Age of Our PatientsThe effect of age on prognosis is shown in Table IV andthis experience conforms to that of others, particularly inregard to infants under the age of 1 year where survivalrates of 80 - 85 % are commonly obtained. Indeed, it is nowfelt that these infants should be separately classified fromTABLE IV. EFFECT OF AGE ON PROGNOSISNo. of Sur- SurvivalAge cases vivors rateLess than 1 year 3 3 100%)1951 -'96712 - 35 months 20 10 50%More than 3 years 22 6 27%Totals 45 19 42%Less than 1 year 2 2 100%)1968_197012 - 35 months 9 5 55%More than 3 years 9 5 55%Totals 20 12 60%the point of view of prognosis and treatment. An unusualfeature of our series is the small proportion (5 %) of casesunder 1 year old. This has improved to 10 % since thenew regime was introduced in 1968.The Advanced Stage of the TumoursThis is illustrated by staging the disease according to thescheme suggested by the Wilm's tumour study group in theUSA (Table V). Note that 33 % of our cases were beyondstage 11, i.e. complete surgical removal was impossible.Also note the marked differences in survival rate betweenthe various stages and that with the new regime 1 patientwith stage IV disease is alive and well after 8 months..The Poor General Health of Our PatientsMalnutrition was common and in 60% of our cases thehaemoglobin concentration was below 9 g/ 100 m!' Further-more, 3 of the children had active tuberculosis whilegastro-enteritis was extremely common in the youngerpatients. These factors rendered the children poor risksStageJ11IIIIVVNo. ofcases19111041Survivors Survival rate12 63%5 45%2 20%0 00 019 42%6 86%3 60%2 50%1 33%0 012 60%1951 - 19671968 - 1970

The management of Wilms' tumour

This report is based essentially on 45 patients with Wilms' tumour treated during the period 1951 - 1967 with comments on a modified regime in 20 patients treated since 1968.During the period 1951 - 1967 the standard treatment was nephrectomy and radiotherapy; cy:oxics were added from 1959. The over-all long-term survival was 42%, but all infants under the age of 1 Year have survived. Cytoxics increased the over-all survival rate from 19% to 55%. Although we aimed at giving post-operative irradiation only, 10 patients received pre-operarve therapy because of the enormous size of their tumours and/or malnutrition. Eight of these patients have survived.In view of the above, all patients, excepting infants under 1 year, have received pre- and postoperative X-ray therapy since 1968. We have also modified the cytoxic regime and all patients have been given repeated courses of actinomycin 0, while those with metastases or recurrence have also received vincristine. The over-all survival rate to date is 60%

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The management of Wilms' tumour

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