tail the experience with radiation induced neoplasms in children treated for retino- blastoma in the Retinoblastoma. Clinic of the. Institute of Ophthalmology and.
VOL.
No.
105,
3
RADIATION EXTERNAL By
ROBERT
INDUCED NEOPLASIA BEAM THERAPY FOR WITH RETINOBLASTOMA*
H. SAGERMAN, M.D.,t
M.D.,t J. ROBERT CASSADY, ROBERT M. ELLSWORTH,
T
HE nant
occurrence
of
neoplasms
benign
and
following
YORK,
NEW
has been previously documented radiologic literature.”35”2’18”9’22 Reese et al.,’4 Forrest,7 and, more recently, Soloway2#{176} have recorded instances of neoplasia following irradiation for retinoblastoma. The purpose of this report is to detail the experience with radiation induced neoplasms in children treated for retinoblastoma in the Retinoblastoma Clinic of the Institute of Ophthalmology and the Radiotherapy Division of the ColumbiaPresbyterian Medical Center; 2! cases are presented, i I for the first time, including the previously unreported development of thyroid carcinoma in 2 patients treated with radium brachytherapy. The incidence of radiation induced neoplasia is correlated with dose, the latent period until the clinical appearance of the radiation induced neoplasm determined and correlated with dose, and the decreased risk of this complication with current treatment methods, are emphasized.
Fiftieth
Annual
Meeting
of Radiology, Division Medical Center, New
of the
American
of Radiotherapy,t York, New York.
YORK
During treatment From 1930 by Reese With this was
68 were lost to for 5 year an-
given
these 3 years, three general policies have been followed. to 1945, the technique described and his associates’4 was used. method, orthovoltage radiation to
an
ipsilateral
direct
lateral
field and to a contralateral oblique nasal field using a 3 cm. diameter cone. An exposure dose of 7,000-9,000 r was given to each field, for a combined exposure dose of 14,000-I 8,ooo r (approximately ii ,ooo14,000 r tumor dose). Beginning in 1945, most patients were treated with the same technique but with a reduction in the combined exposure dose to 7,5000-8,000 r (approximately 6,ooo-6,oo r tumor dose). The third policy began in the early I950s with the use of a single direct lateral field and the delivery of a tumor dose of 3,500-4,500 r; this was initially accomplished with kilovoltage equipment until a megavoltage unit became available in 1957. Several patients received a second course of radiation therapy following initial treatment failure, with occasional tumor control and longterm survival. Treatments have been given on a three times a week basis throughout. Field size has varied from a 3 cm. diameter circle to a 4 cm. X 5 cm. rectangle. With kilovoltage radiation the dose in compact bone is approximately 2.! times, and the dose in the “soft tissue” component of bone approximately i.6 times, the soft tissue tumor
Six hundred and twenty-five patients were registered in the Retinoblastoma Clinic from 1930 through 1963; 92 were seen before i86 from 1946 through 1954, and 37 thereafter. Of these, 397 received radiation therapy; the remainder were treated surgically, either for unilateral disease or when disease was so advanced that no hope of retaining vision remained. In 243 of these 397, follow-up data are available for g or more years; of the remainder, 81 died of retinoblastoma, 5 died at the
TRETTER,
METHOD
MATERIAL
#{149} Presented
PATRICIA
of intercurrent disease, and follow-up or are not eligible alysis.
malig-
radiation
therapy in the
From the Department Columbia-Presbyterian
M.D.,t M.D4
and
NEW
FOLLOWING CHILDREN
Radium and
529
Society, the
Institute
Miami
Beach,
Florida,
of 0phthalmoIogy
April
7-11,
Retinoblastoma
1968. CLinic,
of the
R.
530
H.
J.
Sagerman,
R. Cassady,
P. Tretter
I
TABLE
HISTOLOGIC
three
No.
9
Fibrosarcoma
2
Sarcoma, unspecified Thyroid, papillary-follicular Squamous cell carcinoma Histiocytoma, malignant Mesenchymoma, malignant Rhabdomyosarcoma Basal cell carcinoma
2 2
2
fibrous
i
I i i
21
through
M.
general
tumor
Osteosarcoma
18-20
R.
Ellsworth
MARCH,
treatment
1969
policies
noted
above. There has been a significant reduction in the risk of developing a radiation
DIAGNOSIS
Histopathology
dose.8
and
Currently, 3,500 rads is reached in days using 22.5 mev. photons a 3 cm. X4 cm. lateral field.
with
the
lower
doses
now
in
use.
Development of radiation neoplasm carries a grave prognosis. Only 6 of these 2J patients are now alive. Three of these 6 have required several operations plus radiation therapy to control disease; one boy is clinically stable 8 months after irradiation for a nonresectable sarcoma involving the brain. Table v summarizes the pertinent information for each patient. As previously noted, 2 girls in this series were treated by means of radium tubes on a tray which was placed lateral to the eye for a predetermined period of time. Both patients subsequently developed histologically proven adenocarcinoma ofthe thyroid.
RESULTS
A second 23
malignant
patients.
veloped field, diation
Two
in the and
are induced
cases
femur, not
tumor outside
the to leaving
de-
treatment
represent 2!
CASE
nosed
ra-
cases
analysis. A histologic diagnosis was established in each patient (Table i). There were 10 males and i i females; the sex ratio in retinoblastoma is I : i. The age at diagnosis of retinoblastoma in these patients ranged from 6 weeks to 6 years with a mean of 2 years (Table II). The latent period from conclusion of radiation therapy to the initial signs and/or symptoms of the second neoplasm ranged from 4 to 30 years, with a mean of I I years. The greatest number of cases appeared in the fifth posttreatment year (Fig. i). There was no apparent correlation between dose and latent period. Table iii shows the incidence of neoplasia development correlated with dose for those children followed for a minimum of years. Although the numbers are small, the incidence seems to fit a quadratic rather than a linear relationship. The summary of modified life table analysis of all patients receiving radiation therapy is presented in Table iv. The three time periods analyzed correspond to the for
REPORT
in
of osteosarcoma
thought tumors,
appeared
i6,
I.
and 1930
left
ifl
orbit
nerve
OF
CASES
Bilateral retinoblastoma the
left
a
year
was
eye
enucleated
old girl.
deemed
was infiltrated
examination. for
noted.
This
the
with
right
as
tumor
of the the
was
Four
optic
on histologic
therapy eye.
diag-
December
Exenteration
necessary
Radiation
taken tions
was on
radium
underapplica1931 to
(I/wk.) were made in January, a total of 6,ooo mg. hr. The radium was filtered with 3 mm. brass and was situated approximately 3 cm. lateral to the patient’s right eye. The approximate exposure dose at the eye and thyroid was 3,600 r and 400 r, respectively. No other history of radiation exposure in utero or childhood could be discovered. The patient was well until age 14 years (May, 1941) when left cervical lymphadenopathy was progressed
and
left thyroidectomy and section were performed. TABLE AGE
AND WITH
Age
(yr.)
SEX
OF
INDUCED
I
a
1941,
discx-
II
DISTRIBUTION
RADIATION
