JANUARY,

WILMS’ B.

By

TUMOR: TREATMENT

SCHNEII)ER,t

IL

H.

THE

HE

introduction

an

which

may

tissues

led

Dactinomycin

of

increasing

awareness

follow us

to

irradiation

NEW

radiotherapy

tomy

complete

to the

tumor

Forty-four

tion

AND

patients

(37

are

shown

patients) Pain, Weight loss, Pallor, etc.

Gross Hema-

tuna

Presenting Associated

follow-

28 9

4

5

‘2

7

37

6

12

METHODS

seen

age

in Figure

and i.

the

during

sex

the opposite kidney in the presence of widespread intra-abdominal disease. The signs anti symptoms of disease in the 37 on

distribu-

Eighty-five

per

cent of the patients were under 5 years of age at the time of diagnosis, with a range from 6 days to 10 years 7 months. The median age was 31 months and the average age 42 months. The tumor arose in the right kidney in 2.3 cases, the left in 20, and the involved side could not be determined in i . No case of primary bilateral Wilms’ tumor was encountered, although I patient had a nodule

patients are

The

in Table

congenital

ciation

with

Table did

mi tially

treated

shown

II.

not

The alter

at our

anomalies presence the

There have the treatment

institution

i.

found

nephroblastoma

in asso-

are

shown

of congenital

survival

in

defects

rate.

been only program

2

major during

changes these

in 14

II

TABLE ASSOCIATED

(0

I SYMPTOMS

Mass

Total

were

The

19521965.

bed,

SAN’I’tTLLI

of

removal?

MATERIAL

years

renal

V.

AND

normal

experience

1’.

TABLE SIGNS

the Combined Pediatric Tumor Group of the Babies Hospital, Columbia-Presbytenan Medical Center, with Wilms’ tumor. Two questions were posed: (i) Has the use of Dactinomycin improved the survival rate? (2) What is the value of postnephrecing

and

\VOLFIi,

A

YORK

sequelae

of

the

YORK,

OF

and

of the

review

J. A.

SAGERMAN,t NEW

T

EVOLUTION PROGRAM*

5970

CONGENITAL

DEFECTS

-

mole 9female

9

ZZZI

No.

25

8

#of

7

Cases

6

7-

3-

I

0-I

/

*

Presented

1.

Age at the

uterus

-2

Inguinal 2-3

3-4

4-5

Age FIG.

heart

Bicornuate

1*

defect (pre-atrial sinus) and low set ears duct

1*

Persistent vitelline Horseshoe kidney Aniridia Undescended testicle Supernumerary digits

54-

2

Congenital

anti

Annual

of Radiology,t York, New

6-7

7-8

1*

1*

hernia

ho-u 1

I

8

(years)

sex distribution:

Fifty-first

From the Departments the Babies Hospital, New

5-6

1*

Meeting

*

patients.

4

of the

Pediatrics,

American and

Radium

Surgery,

Died

Society, Columbia

York.

92

of

tumor.

Philadelphia, University

Pennsylvania, College

of Physicians

April

r-o, and

1969. Surgeons,

and

VOL.

lOS,

Wilms’

No.

years: the substitution of megavoltage for kilovoltage radiotherapy and the introduction of Dactinomycin chemotherapy. Diagnostic work-up was accomplished quickly and manipulation of the mass was minimized. Operation was usually undertaken within 24 hours, and surgery was directed to complete tumor removal with nephrectomy and resection of intra-abdominal spread when present. Irradiation of the “tumor bed” commenced after a stable postoperative state was reached, usually 5-7

days

after

operation.

A tumor

dose

of

Tumor

93

The other irradiation

had and

been one

treated with surgery, day course of Dactinomycin. The sole survivor was 24 years old at the time of gross surgical removal of the abdominal mass, radiotherapy to the tumor bed and chest, and chemotherapy; the tumor progressed despite 2 courses of Dactinomycin given 6 weeks apart but disappeared during 20 weeks’ treatment with intravenous Vincnistine. This boy is now alive without evidence ofdisease 5 months after operation and 38 months following the last dose of Vincristine.

rads was delivered in 3-4 2. INCOMPLETE REMOVAL weeks with kilovoltage equipment; when There were 10 patients in whom residual megavoltage units became available in i 957, tumor was known to be or thought to be the dose was raised to 3,000-4,000 ratis in 3-4 weeks. The full width of the vertebral present at completion of surgery. This includes those with intra-abdominal metascolumn was irradiated, and the iliac crest tases, local tumor invasion, and cases in was excluded from the field when possible. which the tumor was inadvertently entered Prior to 1961, chemotherapy was given only for metastatic disease. Since 196!, during surgery resulting in tumor contamiDactinomycin has been given to all panation of the penitoneum. All received posttients, usually beginning I day before or on operative irradiation. There were survi3 never developed methe day of surgery. Multiple courses of #{231}vors in this group; tastases and are alive at 13, 15, and 16 days each, 75 micrograms/kilogram per years, respectively. In the fourth, pulmocourse, have been utilized. Seven of the 4 patients reviewed will be nary metastases appeared 4 months after treatment; these were irradiated and there excluded in the discussion of results. Six had receiveti initial treatment elsewhere has been no recurrence in the ensuing i6 years (Fig. 2). and the 7th proved to have a benign Wilms’ Five of the 6 patients who died were mitumor histologically. 2,500-3,000

tiallv RES

U LTS

The remaining 37 cases have been divided into 3 categories according to the extent of disease at the time of diagnosis: (i) those with metastases beyond the pentoneal cavity; (2) those with disease limited to the abdomen in whom total removal could not be accomplished; and (,) those in whom total excision was thought to have been accomplished. I.

DISTANT

METASTASES

Three patients presented with pulmonary metastases. Two died within months of diagnosis with disseminated disease. One, treated by irradiation alone, was considered inoperable because of liver involvement.

treated

with

surgery

and

radiother-

(Fig. 2). The sixth, the only one in this group to receive prophylactic chemotherapy, developed metastases 2 months after a first course of Dactinomycin; these could not be controlled with triple chemotherapy ( methotrexate, cytoxan, dactinomycin). apy

3.

TOTAL

EXCISION

Gross total removal of disease was accomplished in 24 patients (Fig. 3). Sixteen are alive and 8 have died. One-half of the survivors were treated with surgery and irradiation, without chemotherapy, all prior to I 96 I . Seven of these have remained disease-free. One developed a solitary lung metastasis 25 months after treatment, was managed by a combination of Dactinomy-

Schneider,

94 INCOMPLETE

Sagerrnan,

\Volff

REMOVAL

Eight

f0 olive (SoR)

dead 6

4 I no

1 I

‘

3

1

(S.Rl

chest mets

dmeose

IS’R#{149}Cl

5

IR)

chest mets

I #{149}

obd. eotensson

(R)

(RI

3

2

cheat

of

-

obd.

mets

nitiol site of dissemination

radiotherapy; of dissemination

none

on the patient, Dactinomycin.

this

later

nephroblastoma.3

primary

but

than

in 2

year

not

GROSS

TOTAL

survival

led

clay treated

in

to

the with

for

more

death rate data indicate

is a statistically evaluation

5 shows

in

failure

followed

cumulative 4. These

perfect

Figure

treatment.

6o,

FACTORS

been

The Figure

years.

2

renal

postoperative was being

have

plotteti that a

after

7th who

patients

They 48,

Dactinomvcin and

PROGNOSTIC

All than

is without This tinpatient in

2 years

received

Septicemia

8th

44,

died, 7 died of dis3). Six were treated followed by irradiation

resection

death

42,

(Fig.

other

addition.

shown

3).

who

disease

the

have

39,

30,

proto sur-

(Fig.

for

1970

received

gery and evidence

anti

metastasis

survivors

in addition

cm and surgical resection, anti disease 6 years after recurrence. usual case represents the only develop

i6

Dactinomycin

seminated

2. The initial site of failure was outside the treatment field in all cases, although recurrence within the radiated volume appeared later in a few. This suggests that clinically undetectable metastases were present before completion of irradiation. (S = surgical resection ; R = radiotherapy; C=chemotherapy; Cp=prophylactic chemotherapy; ? = unknown.)

to

the

JANUARY,

IR’Sl

11G.

series

tulli

phylactic

by surgical .

San

have been followed 6 and 8i months. Of the 8 patients

I

I

I

ail

valid

of

survival

rate

is

cure vs.

for

age

REMOVAL

24

alive

dead

16

8

(S+R)

with

(S+R4Cp)

8

8

disease

without

7

disease

I (septicemia) (S+Cp)

no

I disease 7

1 chest

(S+R)

mets.

6

I

1 (S+R+Cp)

(S+C)

chest’ (R+C) chest

ABD

3 (R)

I

2

/\ (R)

.

FIG.

- initial 3. See

site

legend

?‘

(R+C)

of dissemination of Figure

2.

at

VOL.

io8,

Wilms’

No.

diagnosis. In contrast there is no statistically in survival at any age. seen in other reports.13”5 that this might be due patients by Dactinomycin, prove to be true in our No

statistically

to earlier reports,’#{176}”8 significant difference Similar findings are At first we thought to salvage of older but this did not small group.

significant

difference

was

without

this

95 too

80 0/,

Survival

finding

#{190}

60

40 3/7

among Females

found

-

(P

the other clinical features studied. fared somewhat better than males, 14/25 vs. 9/19 surviving. Survival in the 3 patients in whom the side of origin could be determined was better for right-sided involvement (14/23) than for left-sided involvement (9/20). In addition, females with right-sided tumors had a survival rate almost twice as great as females with left-sided tumors (10/14 vs. 4/I i), whereas no such difference was found for males (4/9 vs. Of the 37 patients treated initially by us, those with microscopic evidence of vascular invasion had a poorer survival rate (6/i ) than those