Head & neck cancer comprises several different malignant tumors that develop in throat, larynx, nasal cavity, sinuses, lips, or mouth. Patients with refractory H&N cancer have poor prognosis, with response rates being less than 40% for chemotherapy and less than 20% for newer immunotherapies. Cure rates remain poor also with irradiation or salvage surgery.
Interstitial photodynamic therapy (iPDT) is a promising treatment for H&N cancer where optical fibers are placed within the target tumor to deliver deep intratumoral illumination for bulky disease. It is approved in Europe for palliation of patients with advanced, refractory H&N cancer using temoporfin as a photosensitizer, while Photofrin® has been approved for other indications in USA and is being studied for H&N cancer. However, optimal light irradiance and the contribution of light-induced tissue heating to tumor response are poorly understood aspects of iPDT. The aim of this study was to optimize these important light delivery parameters for H&N cancer.
In vivo experiments consisted of test subjects with murine squamous cell carcinoma tumors being treated with either a single 2 cm long cylindrical diffuser or two diffusers inside transparent catheter(s) inserted into the tumor. Cylindrical diffuser fibers were connected to Modulight ML6500 laser at 630 nm delivering 60-400 mW/cm irradiance and 100 J/cm2 fluence (1-fiber illumination) or 60-150 mW/cm and 540 J/cm (2-fiber illumination). The temperature changes during illumination were assessed by magnetic resonance thermometry and the cure rates were compared between Photofrin® PDT and light-induced tissue heating (no photosensitizer).
Study results with setting described above were used to design an iPDT pilot study in larger test subjects with H&N tumors comparable in size and location to clinical setting. Since the tumor volumes were >8-10 times larger than in the setting in smaller subjects, 6 illumination fibers delivering irradiance of 200-250 mW/cm were used for each tumor. Image-based treatment planning was used to guide the placement of the cylindrical diffusers inside the tumor.
Illumination with one fiber
Some level of tissue heating was observed at all used light intensities. At lower intensities (60-100 mW/cm), less than 5% of the tumor was subjected to >60 ⁰C temperature, a point where irreversible thermal damage will immediately occur (photothermal ablation). At intensities of 150-200 mW/cm, 15-20% of the tumor was at >60 ⁰C temperature. At 400 mW/cm, which is FDA-recommended light irradiance for iPDT, a substantial portion of the tumor, up to 60%, was above 60 ⁰C.
Illumination with two fibers
Test subjects treated with 2-fiber approach had significantly higher photothermal effect in tumors with 100 and 150 mW/cm compared to 60 mW/cm. 25% cure rate was achieved with 60 mW/cm for tumors with and without Photofrin®. However, light intensity of 100 mW/cm resulted in significantly higher cure rate of 70% with Photofrin® PDT as compared to cure rate of 40% without Photofrin®, demonstrating that iPDT is more effective than light alone.
iPDT also in larger H&N test subjects was successful while generating significantly less photothermal effects compared to smaller test subjects. An effective local control was achieved in 4 out of 5 treated subjects (80%). In one subject that had regional recurrence, the minimum irradiance was significantly lower than used for other subjects.
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Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer
Gal Shafirstein, David A. Bellnier, Emily Oakley, Sasheen Hamilton, Michael Habitzruther, Lawrence Tworek, Alan Hutson, Joseph A. Spernyak, Sandra Sexton, Leslie Curtin, Steven G. Turowski, Hassan Arshad & Barbara Henderson
British Journal of Cancer, 2018, 119
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