Interstitial Photodynamic Therapy of Head and Neck Tumors
I. Bing Tan
INTRODUCTION
Photodynamic therapy (PDT) is a technique that uses a combination of a systemic photosensitizing agent with selective activation of the agent at the tumor location by delivering a certain wavelength of light. The activation of the drug induces oxidative breakdown, producing reactive oxygen species, which in turn triggers a cascade of oxidization of biomolecules, eventually leading to cell destruction. PDT shows its biologic effect through several mechanisms including direct cell apoptosis, necrosis through vascular shutdown, and, in the long term, inducing tumor-specific immune responses.
Our Institute and several other research groups are developing this technology to apply to the treatment of cancer of the head and neck. One of the limitations of PDT is the depth of penetration of light. When tumors are illuminated from the surface, the therapeutic effect is observed 8 to 10 mm deep with temoporfin-mediated PDT. This depth varies with different photosensitizers. Many of the cancers of the head and neck and especially recurrent cancers are deeper than 5 mm, which is our cutoff depth for surface illumination leaving a safety margin of at least 3 to 5 mm. To overcome this adversity, light sources can be implanted in the cancer.
HISTORY
Previous treatments to the neck area need to be questioned in detail to ensure that any conventional treatment is not applicable. Diseases that might be exacerbated with light such as psoriasis or systemic lupus erythematosus should be ruled out before the patient is considered a PDT candidate. Swallowing function and difficulties with speech should be questioned to anticipate further problems after the treatment.
PHYSICAL EXAMINATION
The location of the cancer and its relation to vital structures should be evaluated with direct examination and flexible endoscope. During examination, special attention has to be given to any possible synchronous tumors of the aerodigestive tract. The neck should be palpated to rule out any regional lymphatic metastasis.
INDICATIONS
There is not enough evidence yet to propose iPDT as a curative treatment for primary cancers. The main application of iPDT thus far is in the treatment of cancer in cases where standard treatment methods are no longer applicable or would cause unacceptable morbidity that would incapacitate the patient. The best
examples are patients with multiple primary cancers. These patients have usually undergone extensive surgical resection of upper aerodigestive tract cancer with reconstruction, often in combination with post operative (chemo) radiation. Sometimes they even had another surgical resection or reradiation for recurrence or a second primary cancer. In such cases, the area is so extensively operated and radiated that no further treatment option is possible in case of another primary cancer, except for palliative chemotherapy. Systemic treatments for localized cancer such as chemotherapy can be avoided by treating these patients with iPDT, provided that there are no distant metastases. iPDT has several advantages in such situations. The treatment is local, thereby avoiding systemic side effects. It is executed in one session; it can be repeated as necessary. As experience builds up and methods become refined, iPDT may take its place as a primary treatment option.
examples are patients with multiple primary cancers. These patients have usually undergone extensive surgical resection of upper aerodigestive tract cancer with reconstruction, often in combination with post operative (chemo) radiation. Sometimes they even had another surgical resection or reradiation for recurrence or a second primary cancer. In such cases, the area is so extensively operated and radiated that no further treatment option is possible in case of another primary cancer, except for palliative chemotherapy. Systemic treatments for localized cancer such as chemotherapy can be avoided by treating these patients with iPDT, provided that there are no distant metastases. iPDT has several advantages in such situations. The treatment is local, thereby avoiding systemic side effects. It is executed in one session; it can be repeated as necessary. As experience builds up and methods become refined, iPDT may take its place as a primary treatment option.
CONTRAINDICATIONS
Since iPDT is a local treatment, systemic disease with distant metastasis is not suitable. Tumors invading a major blood vessel have a risk of bleeding after iPDT. The tumor has to be technically suitable for iPDT. This is explained later in the text.
PRETREATMENT PLANNING
The main purpose of preoperative evaluation is to determine whether the entire gross tumor volume (GTV) can be treated with PDT. Therefore, the recurrent or residual disease should be locoregional without distant metastasis. The screening protocols for distant metastasis vary from center to center. Chest radiographs, chest computed tomography (CT) scans, abdominal ultrasound (US), bone scintigraphy, and whole body positron emission tomography (PET) are methods that can be employed to rule out distant metastasis.
Once it is determined that the recurrent disease is locoregional, the cancer has to be adequately visualized for treatment planning. Magnetic resonance imaging (MRI) is the imaging tool of choice for oral cavity and oro-/nasopharynx cancer providing the clearest delineation of the neoplastic tissues. MR images help us to determine if technically all of the cancer can be implanted with light sources and if iPDT would cause a hazard to vital structures, for example, if there is a risk of carotid blowout. In case MRI is not possible (e.g., claustrophobic reaction), PET registered CT can be used for this purpose.
US of the neck combined with fine needle aspiration (FNA) biopsy helps to stage the regional disease.
PRETREATMENT COUNSELING
The photosensitivity caused by systemic photosensitizers requires that the patients receive adequate counseling to prevent complications due to light exposure. The duration of photosensitivity is dependent on the photosensitizer and can range from a few hours to 6 weeks. The agent that we use in our institute, temoporfin, has a photosensitivity of 2 weeks. The patients receive instructions about avoidance of light. Every day, the patient can be exposed to more light according to the guidelines provided to the patient. The patients are supplied with a light meter to measure ambient light before the procedure. They can measure light in their living quarters and adapt the brightness by hanging extra curtains, changing the light bulbs to less powerful ones, or simply avoiding the too bright rooms. The patients keep the light meter during the posttreatment period to be able to measure and adapt the ambient light. After 4 days, normal room lighting can be easily tolerated. However, daylight has to be avoided for at least 3 weeks.
The patients also receive information about airway management, feeding, and other aspects of the postoperative course.
SURGICAL TECHNIQUE
Treatment Planning
It is essential that the entire GTV plus at least 5-mm margins around the cancer are adequately treated. Having a simulated (pretreatment) plan and the means to execute it helps the clinician immensely.
In the oral cavity and oropharynx level, MR images generate the clearest impression of the cancer. The planning is very similar to that of ionizing brachytherapy. Customized brachytherapy software is used to plan iPDT. The point sources of radiation are replaced by linear array of light-emitting point sources produced by a linear diffuser. Various photosensitizers have various activation wavelengths. Treatment light wavelength is
one of the factors that determine the penetration of light and therefore the treatment depth in regard to the light source. Temoporfin has an activation wavelength of 652 nm (red light). The mean treatment depth is 8 mm. The light sources are planned to lie parallel to each other, at a distance of not >15 mm, to provide complete coverage of GTV plus margins. The planning provides us with an adequate idea of the number of light sources necessary to be implanted, their corresponding lengths and position. The illumination phase can be simulated; in other words, the light sources can virtually be turned on, to see if there is any geographic miss, which can thereafter be corrected by modifying the planning (Figs. 11.1 and 11.2).
one of the factors that determine the penetration of light and therefore the treatment depth in regard to the light source. Temoporfin has an activation wavelength of 652 nm (red light). The mean treatment depth is 8 mm. The light sources are planned to lie parallel to each other, at a distance of not >15 mm, to provide complete coverage of GTV plus margins. The planning provides us with an adequate idea of the number of light sources necessary to be implanted, their corresponding lengths and position. The illumination phase can be simulated; in other words, the light sources can virtually be turned on, to see if there is any geographic miss, which can thereafter be corrected by modifying the planning (Figs. 11.1 and 11.2).
