Interstitial Photodynamic Therapy of Head and Neck Tumors

Interstitial Photodynamic Therapy of Head and Neck Tumors

I. Bing Tan


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.


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.


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.


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.


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.


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).

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Jun 15, 2016 | Posted by in OTOLARYNGOLOGY | Comments Off on Interstitial Photodynamic Therapy of Head and Neck Tumors

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