Brachytherapy in the Treatment of Head and Neck Cancer
Brachytherapy in the Treatment of Head and Neck Cancer
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), 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]
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.
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.
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. 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.
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. 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.