Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Light application
Reexamination Certificate
1998-06-24
2002-07-09
Shay, David M. (Department: 3739)
Surgery: light, thermal, and electrical application
Light, thermal, and electrical application
Light application
C606S010000, C606S013000, C604S020000, C128S898000
Reexamination Certificate
active
06416531
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to the use of light therapy to destroy abnormal tissue in a tumor, and more specifically, to the use of multiple light sources disposed at spaced-apart treatment sites within a tumor to render the therapy.
BACKGROUND OF THE INVENTION
Abnormal tissue in the body is known to selectively absorb certain dyes that have been perfused into a treatment site to a much greater extent than surrounding tissue. For example, tumors of the pancreas and colon may absorb two to three times the volume of these dyes, compared to normal tissue. Once pre-sensitized by dye tagging in this manner, the cancerous or abnormal tissue can be destroyed by irradiation with light of an appropriate wavelength or waveband corresponding to an absorbing wavelength or waveband of the dye, with minimal damage to normal tissue. This procedure, which is known as photodynamic therapy (PDT), has been clinically used to treat metastatic breast cancer, bladder cancer, lung carcinomas, esophageal cancer, basal cell carcinoma, malignant melanoma, ocular tumors, head and neck cancers, and other types of malignant tumors. Because PDT may selectively destroy abnormal tissue that has absorbed more of the dye than normal tissue, it can successfully be used to kill the malignant tissue of a tumor with less effect on surrounding benign tissue than alternative treatment procedures.
The effectiveness of PDT for treating tumors has become increasingly more evident to the medical community. Each year, numerous papers are published disclosing research that has been carried out to explore how PDT can more effectively be used and to better understand the processes by which PDT destroys abnormal cells. Much of the prior art discloses the use of relatively high powered lasers as an external light source employed to administer the light to a treatment site. Typically, the light from an external laser source is conveyed through an optical fiber to a treatment site on the skin of a patient or to an internal site within the patient's body. Penetration of a tumor by the optical fiber is achieved either through a small incision in the overlying dermal layer, or directly, if the tumor is surgically exposed.
Most applications of PDT are conducted using a single optical fiber to provide the light therapy. An optical fiber used to render PDT may include a diffuser on its distal end to enhance the radial distribution of light from the fiber. Light emitted through the diffuser more fully illuminates a treatment site within a tumor in which the optical fiber has been inserted.
Research has been conducted to measure the penetration depth of light into tissue as a basis for assessing the volume of tissue that will be affected by the light applied to a treatment site to render PDT. This research has determined that the penetration depth (or a reciprocal value corresponding to the light attenuation of the tissue) depends upon the wavelength of the light, the type of tissue, the direction of irradiation, the oxygenation of the tissue, the striation of the tissue, the perfusion of blood in the tissue at the site, and other physiological and physical factors. Generally, at a wavelength of about 630 nm, the depth of penetration of light into tissue has been found to be between about 0.2 mm and 7 mm, depending upon the type of tissue (as reported in “In Vivo Measurement of the Optical Interaction Coefficients of Human Tumors at 630 nm,” I. Driver, C. P. Lowdell, and D. V. Ash, Phys. Med. Biol., Vol. 36, No. 6, pp. 805-813, Table 3, (1991). Further, this paper reported a large inter-sample variation for the depth of light penetration in the same type of tissue. Tissue of a darker color, such as that of the liver, greatly attenuates light transmission, while brain tissue tends to scatter the light and thus limits light penetration. Generally, longer wavelength light penetrates more deeply, but most of the currently available photoreactive reagent dyes used for PDT have absorption wavebands in the 600-700 nm range.
The limited penetration depth of light in tissue would seem to indicate that light emitted at a single treatment site to render PDT will be effective in destroying abnormal tissue in only a relatively small volume within a tumor. To treat larger tumors, multiple light treatment sites would be expected to linearly expand the volume as a function of the number of light treatment sites used, i.e., the total volume of the effective zone in a tumor treated with the multiple optical fibers should be equal to the product of the volume treated at one site and the number of sites. In a paper entitled “Photodosimetry of Interstitial Light Delivery to Solid Tumors,” M. C. Fenning, D. Q. Brown, and J. D. Chapman, Medical Physics, Vol. 21, No. 7, pp. 1149-1156 (July 1994), reported on research in which both anaplastic and well-differentiated Dunning prostate adenocarcinomas were illuminated in anesthetized Fisher X Copenhagen rats by light from single-fiber and multiple-fiber. illuminators. Each illuminator consisted of a 2 cm laterally diffusing optical fiber placed within a plastic brachytherapy needle implanted into a tumor. The radial falloff of intensity with distance from single fibers was used to determine light attenuation coefficients for various wavelengths, by employing a two-dimensional (2D) photodosimetry computer code. The coefficients were used to calculate relative light intensities in planes perpendicular to the single-fiber and various multiple-fiber configurations. Relative light intensities measured along tumor tracks were compared with those predicted by the 2D photodosimetry evaluation and were found to agree within ±14%, for all configurations of the optical fibers studied. It was noted that at wavelengths equal to and greater than about 700 nm, optical fiber spacings of at least one cm produced relatively uniform light fields (±20%) in tumor planes perpendicular to the optical fibers. At line 32 of the second column on page 1155 of the paper, it is noted that:
For human tumors with light attenuating properties similar to the R3327-H tumor, the heterogeneity of light dose in tumor volumes delivered by a multifiber illuminator with 1.0-cm spacings will be considerably greater than ±20%. Illumination of tumors by such procedures will produce relatively large variations in biological effect by interstitial PDT. Furthermore, to expose all tumor tissue to a minimum light dose required for a specific biological effect, large fractions of the tumor would of necessity be overdosed. While this may not seriously impact upon tumor response, it will limit the volume of solid tumor which can be treated with a specific time by a specific light source. Laser output intensity has not been a limiting factor for the illumination of superficial lesions in clinical studies to date. Nevertheless, to successfully scale up this procedure for the treatment of bulky human tumors, laser output intensity and tumor volume will determine the time required to deliver a curative light dose.
The paper further concludes that more than seven optical fibers may be required to properly treat a tumor with PDT, to guarantee that adequate light is delivered, particularly to the periphery of a tumor, due to the rapid falloff of light at the edge of the illuminated field. The reference thus teaches or suggests that the effect of PDT on a human tumor, particularly one of larger size, will be limited to the region of the tumor directly viably illuminated by the plurality of optical fibers and implies that it will be necessary to repeat the treatment to different areas of the tumor by moving the plurality of the optical fibers so that direct illumination of a greater treatment volume can be accomplished.
The effects of PDT and the manner in which it destroys tissue are not clearly understood. It is believed that the primary mechanism by which PDT destroys cells relies upon the conversion of molecular oxygen to singlet oxygen and the release of free radicals by the light activated dye. In “How Do
Anderson Ronald M.
Light Sciences Corporation
Shay David M.
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