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.
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).
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.
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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