Light delivery optimization for H&N cancer treatment

Customer case

Roswell Park Comprehensive Cancer Center was founded in 1898 as the first institute in the US devoted exclusively to cancer treatment and research. It is also the place where photodynamic therapy (PDT) was developed in the late 1970s by Thomas Dougherty. The PDT center at Roswell Park is a leader in the use of photodynamic therapy for treating different cancers. Research work includes treatment planning and light dosimetry for interstitial and intraoperative PDT to improve the quality of life and survival of cancer patients who have failed to respond to standard therapies or have no effective treatments currently available.

Modulight products: ML7710 & ML6500

Laser use: Optimization of light delivery parameters for interstitial photodynamic therapy for Head & Neck cancer.

David Bellnier, PhD

 

Link to the study:

Background

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.

 

Methods

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.

 

 

Results

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.

 

Above figures are from the original publication. Reproduced under Creative Commons Attribution 4.0 International License.

 

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.

 

 

Above figures are from the original publication. Reproduced under Creative Commons Attribution 4.0 International License.

 

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.

 

Example case of iPDT that resulted in complete eradication of the tumor.

Images from the original publication. Reproduced under Creative Commons Attribution 4.0 International License.

 

Conclusions:
It was shown that some level of heating during iPDT is produced as a byproduct during the illumination and contribute to treatment effect. Photofrin®-mediated PDT dominated the treatment effect at lower irradiances while temperature increase became more pronounced at higher irradiances. Two-fiber illumination approach resulted in higher cure rates at higher irradiances and iPDT was shown to be more effective than light only. A significant temperature increase was not seen in larger test subjects but cure rates still remained high, suggesting that the temperature increase indeed is a byproduct of iPDT and not the main therapeutic component. This is a promising finding for clinical translation and results found in this study were used to design a multi-center phase I/II clinical study to evaluate iPDT with Photofrin® in the treatment of patients with locally advanced H&N cancer.
Funding:
This work was supported in part by National Cancer Institute of the National Institutes of Health under award number R01CA193610 to Gal Shafirstein, PO1CA55791 to Sandra Gollnick, and by Roswell Park Comprehensive Cancer Center Support Grant P30CA16056.

 

Related Modulight products and Services

 

Related Publications

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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