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Brachytherapy in the Treatment of Head and Neck Cancer

Brachytherapy in the Treatment of Head and Neck Cancer

ABSTRACT: Brachytherapy is a therapeutic modality that may provide a significant improvement in the therapeutic ratio when appropriately applied, and hence, is an appealing treatment strategy for the head and neck. For several tumor sites in the head and neck, the use of a brachytherapy implant has been demonstrated to be effective and is optimally provided within a multidisciplinary team setting. This enables meticulous attention to technical and treatment-related factors that have been demonstrated to influence the therapeutic ratio for low-dose-rate implants. Recent technologic advances have enabled the study of promising high-dose-rate and pulsed-dose-rate afterloading brachytherapy techniques, in an attempt to expand the role of brachytherapy in the head and neck. These techniques minimize radiation exposure hazards while offering the physical and biologic advantages of brachytherapy. Issues pertinent to members of the brachytherapy team providing multidisciplinary care of the implanted head and neck patient are discussed. [ONCOLOGY 16:1379-1395, 2002]

Brachytherapy has a significant role in the management of head and neck
squamous cell carcinoma (SCC),[1] largely due to the importance of locoregional
control and the desire to minimize treatment-related functional deficits and
preserve quality of life. In addition, the ongoing risk of second malignancies
and locoregional recurrences in the head and neck requiring reirradiation make
brachytherapy implants particularly appealing.

The use of a brachytherapy implant affords a unique approach to local dose
intensification, improving the likelihood of functional organ preservation and
minimizing treatment morbidity as a result of reduced irradiation to the
surrounding normal tissues. In early-stage lesions, where the risk of nodal
metastases is low, brachytherapy may be employed definitively or in an adjuvant
fashion following surgery. In more advanced lesions, it is often combined with
external-beam radiation therapy (EBRT) of the head and neck. The ability to
provide specific, intensive local irradiation also permits the selective use of
brachytherapy in the setting of recurrent or second head and neck SCC occurring
within a previously irradiated region.

The optimal delivery of a brachytherapy implant necessitates a collaborative
multidisciplinary team approach. This should involve a radiation oncologist
trained in brachytherapy techniques, a head and neck surgeon and an oncologic
nurse familiar with issues specific to brachytherapy implants, a physicist
trained in brachytherapy treatment planning, and a dental surgeon experienced in
radiation complications and the fabrication of spacers and lead-embedded
prostheses. Such a team permits a smooth and efficient integration of treatment
modalities, which may influence local control rates.

This review will elaborate on the current indications for brachytherapy in
the head and neck, highlighting multidisciplinary issues pertinent to achieving
these therapeutic goals. Technical aspects of brachytherapy are beyond the scope
of this review, and the reader is referred elsewhere.[2-7]

Basic Principles

Patient Selection

Appropriate application of a brachytherapy implant begins with patient
selection. This requires assessment of the patient’s understanding and ability
to comply with the inherent radiation precautions associated with brachytherapy
implants, especially for continuous low-dose-rate implants. Patients should be
selected for their ability to provide baseline self-care needs in addition to
treatment-related needs, such as the care of a tracheostomy, nasogastric feeds,
and a patient-controlled analgesic pump, as indicated.

Patients subject to periods of confusion and disorientation may not be
suitable for this mode of therapy. The potential for alcohol or narcotic
withdrawal should be addressed to avoid complications with the delivery of the
implant. Age alone is not a contraindication, but associated comorbidities may
preclude the older patient from complying with the additional responsibilities
noted.

Risk-Benefit Assessment

Considerations of the indications and the relative risk-benefit ratio of an
implant require an assessment of not only the location, size, and extent of the
tumor volume, but also of organ function, and hence, the appropriateness of an
organ-preserving strategy. For the head and neck, attention to the status of
oral/dental hygiene is important, with particular regard to the risk of
mandibular osteoradionecrosis. Evaluation by a dentist familiar with these risks
is mandatory. Other factors associated with an increased risk of severe
soft-tissue complications include severe diabetes, liver failure, and
compromised arterial status.[8]

Permanent vs Temporary Implants

The provisional technique should then be selected to enable appropriate
planning and preparation. Several considerations influence the decision as to a
permanent or a temporary implant.

Permanent Implants—Permanent implants, emitting radiation over the
lifetime of their radioactivity, use sources that provide low-dose-rate
irradiation. Suboptimal placement of a permanent implant and the potential
adverse dosimetric effects of organ swelling and movement pose potential risks
for an unfavorable therapeutic ratio. However, a permanent implant affords the
delivery of a very high total dose of radiation and may be advantageous when
implanting complex, irregular surfaces that are not amenable to the placement of
temporary catheter-based implants, ie, where chinking of the catheters is a
significant risk. The judicious use of permanent radiation sources with
low-energy photons, such as iodine-125, may be advantageous when critical normal
structures, such as the spinal cord, are adjacent to the implant.

Temporary Implants—Temporary implants are more commonly applied in
the head and neck, as they permit a more deliberate and accurate placement of
the applicator system without the radiation exposure concerns associated with a
permanent implant. Typically, nylon catheters are used to mimic the desired
position of the radioactive sources, which are subsequently afterloaded with low-dose-rate
radioactive seeds embedded at defined positions within a nylon strand.

This technique affords optimization of the implant dosimetry following
placement of the implant applicator system. Commonly, this involves obtaining
orthogonal plain x-rays of the implant, with dummy seeds placed within the
selected applicator system and digitization of the relative seed positions into
treatment-planning software. Variations in the activity, number of radioactive
sources, loading duration—and for high-dose-rate computer-guided remote
afterloading systems, variations in the dwell time and position—allow for
dosimetric optimization. However, optimization cannot obviate the adverse
dosimetry associated with poor implant geometry.

Temporary low-dose-rate implants also offer several radiobiologic
advantages, including a reduced treatment time, the ability to irradiate a
potentially less hypoxic tumor bed early in the postoperative period, a reduced
adverse influence of hypoxia itself, and exploitation of cell-cycle-specific
radiosensitization. This technique further exploits the differential repair
capacities between tumor and normal tissues, reducing the risk of normal late
complications. However, the risk of exposure to staff necessitates good source
handling skills and strict radiation precautions.

High-Dose-Rate Implants—Alternatively, high-dose-rate sources with
computer-guided remote afterloading significantly reduce the radiation exposure
risks and required precautions. Fractionated radiotherapy is delivered with a
single iridium-192 source fixed to the end of a guidewire that may be variably
stepped along the length of each catheter.

High-dose-rate implants have greater flexibility in conforming the implant
dosimetry to the target volume and yield a relatively more homogeneous dose
distribution, compared to that of low-dose-rate implants. Moreover, as the
delivery of the radiation occurs over a shorter time, it is less subject to the
effects of organ movement. This precise geometric sparing may yield a lower
complication rate. However, concerns remain regarding the risk of increased late
complications from the higher dose rate of radiation.[9] This has prompted
studies to define optimal fractionation schedules to reduce this risk.

Pulsed-Dose-Rate Implants—The use of pulsed-dose-rate radiation has
been studied as a technique to exploit the logistical advantages and reduced
radiation exposure of remote afterloading and the low-dose-rate biologic
advantages that may be mimicked by this technique.[10,11] The physical delivery
system is analogous to high-dose-rate systems but with reduced source
activity. Typically, a medium-dose-rate source is afterloaded to deliver
radiation every hour for 10 to 30 minutes over several days. The optimal
pulse size and pulse interval remains to be determined. Between pulses,
radiation precautions do not need to be in effect, thereby facilitating improved
treatment compliance. This technique remains promising but investigational to
date.[1,12]

Intraoperative Radiation Therapy—An appealing alternative to the use of
temporary implants is the use of high-dose-rate intraoperative radiation
therapy. This technique has the advantage of accurately delivering radiation to
the surgical bed and areas at risk of tumor recurrence, as defined at the time
of the resection. In addition, intraoperative irradiation may optimize the
cytotoxicity of the irradiation, as the tumor burden is at its lowest and the
adverse effects of hypoxia are likely to be less influential than during the
postoperative period. Optimized implant geometry results from the use of
prefabricated commercially available applicator systems that maintain a uniform
plane of catheters, which may then be molded to conform to curved and irregular
surfaces. This modality remains investigational and limited to centers with
expertise in the technique.[13]

Surgical Support

Surgical support is integral to the care of the implanted patient. Assessment
and management of the upper aerodigestive airway is fundamental, particularly if
the implant involves the pharyngeal airway or the base of the tongue, due to the
potential for edema and bleeding. Coordination of the surgery and the planned
brachytherapy implant is crucial for a successful implant. For permanent
implants, surgical exposure of the area for implantation may be required.

Coordination of surgical approach and implant technique is required not only
to optimize the implant geometry but also to reduce the risk of wound
complications. For temporary implants, surgical drains and wound dressings must
be placed so as not to preclude the loading and unloading of any catheters. The
placement of catheters and the wound-closure technique must also be coordinated
to ensure minimal tension and potential distortion of the implant geometry.

In the setting of a neck dissection or when other surgical wounds lie near
implant catheters, we prefer to delay the implant loading for a minimum of
5 days postoperatively. This is due to concerns of increased wound
complications resulting from irradiation of the wound before sufficient
fibroblast proliferation has occurred, as has been observed in the treatment of
extremity sarcomas.[14] Although these concerns remain to be validated in the
head and neck, this time is often required for treatment planning and for the
patient to acclimatize to the increased self-care needs related to the surgical
procedure(s), to maximize their adherence to radiation precautions.

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