Use of Brachytherapy to Preserve Function in Children With Soft-Tissue Sarcomas

Use of Brachytherapy to Preserve Function in Children With Soft-Tissue Sarcomas

ABSTRACT: Pediatric soft-tissue sarcomas are managed with a multimodality treatment program that includes surgery, chemotherapy, and external-beam radiotherapy (teletherapy). The use of teletherapy in young children can result in significant long-term toxicities (especially growth retardation of bones and organs). Brachytherapy, if feasible, is an attractive alternative for the treatment of pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may potentially minimize complications. Aggressive chemotherapy is used to achieve systemic control and tumor shrinkage, thereby facilitating conservative surgery and brachytherapy. The brachytherapy techniques used in children are similar to those employed in adults. Low-dose-rate (LDR) brachytherapy with manually afterloaded removable iridium-192 is commonly used, although it is associated with some radiation exposure hazards. Low-energy radionuclides (eg, iodine-125) and remote afterloading technology have been used to reduce radiation exposure hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without supplementary teletherapy, has produced good local control with acceptable late complications in selected patients with localized tumors. Brachytherapy can also be used as a boost to moderate dose external-beam radiotherapy for more extensive tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate, and intraoperative brachytherapy, has allowed brachytherapy to be given to younger children and infants, but the long-term morbidities of these modalities need to be established. [ONCOLOGY 13(3):361-370,1999]


Of the approximately 8,000 new malignant
neoplasms diagnosed in the United States annually, 2% occur in
children. Soft-tissue sarcomas comprise 6.5% of pediatric malignant tumors.

The management of pediatric soft-tissue sarcomas is a therapeutic
challenge. Treatment of this disorder has undergone a revolution
during the past 2 decades with the initiation of the prospective
Intergroup Rhabdomyosarcoma Study (IRS). Combined-modality treatment
is the standard approach for soft-tissue sarcomas, and one of the
main therapeutic goals is preservation of function.

Current IRS IV guidelines call for the use of external-beam radiation
therapy, or teletherapy (4,140 to 5040 cGy; or, alternatively, 5,940
cGy hyperfractionated at 1.1 Gy twice daily) in all patients, except
those classified as group I within stages I and II (ie, those with
localized, completely resected disease and no regional node
involvement). According to the guidelines, this latter group should
not receive teletherapy. The standard planning target volume
encompasses the gross tumor volume, with a 2-cm margin to allow for
microscopic spread, internal organ movement, set-up error, and
patient movement.[1-3] This results in the delivery of the prescribed
dose to a large tumor volume.

In addition, since the radiation is delivered from outside the
child’s body, teletherapy results in the delivery of a moderate
radiation dose to a large volume outside of the planning target
volume (Figure 1). This may cause
severe late morbidities, especially growth retardation problems,
which can be devastating in a developing child.[4-6] Hence, radiation
therapy is often eliminated from the treatment program, with
resultant decreased survival in the very young child.[6]

The IRS I and II guidelines recommended limiting teletherapy doses to
40 Gy in infants. Doses of 50 to 60 Gy were recommended for older
children, depending on the extent of disease. The analysis of local
control revealed a higher local failure rate for infants in groups I
through IV, although this difference was only statistically
significant (P = .02) for group III patients (ie, those with gross
residual disease at the start of treatment).[6]

Brachytherapy refers to treatment of a tumor at a short distance
using sealed radioisotopes placed inside or close to a tumor. It has
been used to treat childhood cancers in some centers.[7-32] The
planning target volume for brachytherapy is smaller than that for
teletherapy and closely approximates the clinical target volume,
since there is no need to allow for internal organ movement, patient
movement, or set-up errors (Figure 2).
Furthermore, since the dose from brachytherapy falls off at a rate
that is inversely proportional to the square of the distance, the
volume of normal tissues that is irradiated outside of the planning
target volume is minimized (Figure 2),
thereby reducing long-term morbidity.

Compared with teletherapy, brachytherapy has a shorter time course (7
to 8 days) and can be started soon after surgery. The shorter time
course also expedites the integration of systemic chemotherapy, which
is of prime importance in childhood soft-tissue sarcoma.

Techniques Used

The brachytherapy techniques used in children are modified from those
employed in adults. Brachytherapy can be divided, according to the
placement of the radioactive material, into intra-cavitary (inside
body cavities) and interstitial (within tissues). Brachytherapy can
be further subdivided, according to its duration, into temporary (the
radioactive material being withdrawn after a specified dose has been
delivered) and permanent (the radioactive material is left to decay
in the body).

Brachytherapy can also be classified according to the prescribed dose
rate: high-dose rate (HDR) techniques de-liver > 12 Gy/h);
medium-dose-rate (MDR) techniques, 2-12 Gy/h; and low-dose-rate (LDR)
techniques, < 2 Gy/h. Finally, pulsed-dose rate (PDR)
brachytherapy is the administration of remote afterloading
brachytherapy in small pulsed doses of 1 to 2 Gy per interval (1 to 4
hours), over a few days. Table 1
summarizes the differences between the various radiation techniques.

Manually Afterloaded LDR Removable Brachytherapy

This is the most common type of brachytherapy used in children. Nylon
catheters inserted into the target volume with the aid of hollow
needles are then loaded with radioactive sources. A variety of
templates can be used to aid the accurate positioning of the sources
inside the target volume. Custom-built intracavitary vaginal
applicators are generally used for gynecologic sites (standard sized
applicators are usually inappropriate for young girls with
soft-tissue sarcoma). Afterloading of radioactive sources (usually
iridium-192 or cesium-137) is most often done 3 to 5 days after
surgical excision to allow healing to begin.

There is a potential radiation hazard for the nursing staff and
parents associated with the release of radiation in LDR
brachytherapy, particularly in the treatment of younger children and
infants who require constant monitoring. For patients implanted with
cesium-137 or iridium-192, visitor restrictions are required to
minimize radiation exposure of the parents and medical caregivers.
These restrictions can be minimized if a low-energy radioisotope,
such as iodine-125, is used. In these cases, thin sheets of lead
applied over the treated area or standard lead aprons (0.25 mm lead
equivalent) can adequately shield visitors.

Permanent Interstitial Brachytherapy

For permanent brachytherapy, low-activity iodine-125 seeds are
commonly used. These are usually embedded at 1.0 cm intervals in
vicryl suture material and directly sewn into the tumor bed. If there
are gross palpable tumors in the target volume, the iodine-125 seeds
are inserted into the tumor through hollow needles.

The low-photon energy of iodine-125 (28 KeV) makes hospitalization, a
shielded room, and strict visitor restrictions unnecessary.
Nevertheless, it is prudent for the patient to avoid prolonged
contact with pregnant women and children below 18 years of age during
the initial few months of therapy.

Remote Afterloading Brachytherapy

With remote afterloading brachytherapy, the catheters (or
applicators) are inserted into the tumor site, as in the manually
afterloaded technique. They are then connected to the afterloader for
remotely controlled radioactive loading. High-dose-rate, PDR, and
remote LDR techniques eliminate radiation exposure hazards to parents
and medical caregivers. In addition, the radioactive sources in this
equipment are retracted into the main safe during planned
interruptions or in the event of accidental entry into the treatment room.

The treatments are performed over a few days in PDR and LDR
brachytherapy and over a few minutes in HDR procedures. The short
treatment time of HDR brachytherapy obviates the need for prolonged
immobilization and sedation of these young children and infants.
Furthermore, hospitalization is not mandatory, and the procedure can
be done on an outpatient basis. In most remote-controlled
afterloaders, the tumor is irradiated by a single radioactive source
(stepping source) that moves in discrete steps through the tumor. The
dose given is directly proportional to the time (dwell time) the
source spends at a particluar position (dwell position). The dwell
times can be adjusted (decreased to minimize “hot spots” or
increased to minimize “cold spots”) to optimize the
treatment. Hence, the use of the stepping source in remote
afterloaders allows for treatment optimization through the use of
variable dwell times.

Intraoperative HDR Brachytherapy

Intraoperative HDR brachytherapy is a method of delivering a single
large dose of HDR brachytherapy to a surgically exposed tumor site.
Hollow plastic catheters are inserted into special flexible
applicators and connected to the HDR machine. The treatment is
delivered using a single, high-activity iridium-192 source. Normal
tissues are either displaced from the irradiated area or shielded, if
clinically applicable.

The tumor bed is visualized directly, thereby avoiding a geographical
miss. Risk of catheter displacement is also reduced, since the
treatment is given over a short time to an anesthetized patient. The
need for an appropriately shielded operative suite, or alternatively,
the need to transport the anesthesized patient to the radiation
oncology suite limits the use of this modality to very few centers.


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