Proton beam versus photon beam dose to the heart and left anterior descending artery for left-sided breast cancer.

PURPOSE: The purpose of this study was to compare the dose to heart, left anterior descending (LAD) artery and lung between proton and photon beam irradiation for left-sided early stage breast cancer. MATERIAL AND METHODS: Ten women with early stage left-sided breast cancer were treated with breast conserving surgery and radiation. Whole breast radiation was delivered for actual treatment via a tangential technique with deep inspiration breath hold (DIBH) utilizing inverse planned intensity-modulated radiation therapy (IMRT). Each patient was replanned on an Institutional Review Board (IRB)-approved prospective study using en face proton beam radiation with both uniform scanning (US) and pencil beam scanning (PBS) techniques. RESULTS: Both PBS (0.011 Gy) and US (0.009 Gy) proton plans resulted in a significantly lower mean heart dose compared to IMRT (1.612 Gy) (p < 0.05 for PBS vs. IMRT and US vs. IMRT). The Dmean, Dmin, Dmax, and D0.2cm(3) of the LAD with either proton technique were significantly lower (p = 0.005) compared to IMRT. Both US and PBS reduced the mean dose to the lungs compared to IMRT. The coverage of the breast planning target volume was comparable between photon and proton plans. CONCLUSIONS: The dose to whole heart was relatively low in this study of patients treated under conditions of DIBH. However, proton beam radiation was associated with lower minimum, maximum, and dose to 0.2 cm(3) of the LAD, which is the critical structure for late radiation therapy effects, compared to even the most optimized photon beam plan with DIBH and IMRT.

Clinical PDT dose dosimetry for pleural Photofrin-mediated photodynamic therapy.

Significance: Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment. Aim: We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes. Approach: The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients. Results: Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is 4.98 µM, with a median concentration of 4.47 µM. The average PDT dose for all 78 sites is 493.17 µMJ/cm2, with a median dose of 442.79 µMJ/cm2. A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients. Conclusions: The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy.

Three-dimensional printing of the human lung pleural cavity model for PDT malignant mesothelioma.

OBJECTIVE: The primary aim was to investigate emerging 3D printing and optical acquisition technologies to refine and enhance photodynamic therapy (PDT) dosimetry in the management of malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: A rigorous digital reconstruction of the pleural lung cavity was conducted utilizing 3D printing and optical scanning methodologies. These reconstructions were systematically assessed against CT-derived data to ascertain their accuracy in representing critical anatomic features and post-resection topographical variations. RESULTS: The resulting reconstructions excelled in their anatomical precision, proving instrumental translation for precise dosimetry calculations for PDT. Validation against CT data confirmed the utility of these models not only for enhancing therapeutic planning but also as critical tools for educational and calibration purposes. CONCLUSION: The research outlined a successful protocol for the precise calculation of light distribution within the complex environment of the pleural cavity, marking a substantive advance in the application of PDT for MPM. This work holds significant promise for individualizing patient care, minimizing collateral radiation exposure, and improving the overall efficiency of MPM treatments.

A novel investigational preclinical model to assess fluence rate for dental oral craniofacial tissues.

OBJECTIVE: Photodynamic Therapy (PDT) and Photobiomodulation (PBM) are recognized for their potential in treating head and neck conditions. The heterogeneity of human tissue optical properties presents a challenge for effective dosimetry. The porcine mandible cadaver serves as an excellent model and has several similarities to human tissues of the dental oral craniofacial complex. This study aims to validate a novel modeling system that will help refine PDT and PBM dosimetry for the head and neck region. METHODS AND MATERIALS: Light transmission was analyzed through several tissue combinations at distances of 2 mm to 10 mm. Maximum light fluence rates (mW/cm2) were compared across tissue types to reveal the effects of tissue heterogeneity. RESULTS: The study revealed that light fluence is affected by tissue composition, with dentin/enamel showing reduced transmission and soft tissue regions exhibiting elevated values. The porcine model has proven to be efficient in mimicking human tissue responses to light, enabling the potential to optimize future protocols. CONCLUSION: The porcine mandible cadaver is a novel model to understand the complex interactions between light and tissue. This study provides a foundation for future investigations into dosimetry optimization for PDT and PBM.

Validating Homogeneity for a Novel 3-Dimensional Tissue Phantom Modeling System of the Human Maxilla.

Silicon phantom models have been utilized to calculate light fluence in patients being treated with Photodynamic Therapy (PDT). This application can be utilized for other non-ionizing wavelength therapies such as Photobiomodulation (PBM). We have developed a novel protocol to validate homogeneity for 3-dimensional silicon phantom models of the human maxilla. Accurately quantifying the light profiles of human tissue can accommodate for varying optical properties that occur between subjects. More importantly, this can help optimize light fluence dosimetry calculations to achieve intended results. Silicon models of identical composition were fabricated into two different shapes: 1 flat-planar cylindrical shaped model, 2) non-flat planar (3-dimensional) mold of the human maxilla. Fabricating homogenous silicon phantom models continues to be a challenge as micro-bubbles can contaminate the compound during the curing process. Integrating both proprietary CBCT and handheld surface acquisition imaging devices confirmed our results to be within 0.5mm of accuracy. This protocol was specifically used to cross-reference and validate homogeneity at various depths of penetration. These results present the first known successful validation of identical silicon tissue phantoms with a flat-planar surface vs. a non-flat 3D planar surface. This proof-of-concept phantom validation protocol is sensitive to the specific variations of 3-dimensional surfaces and can be applied to a workflow used to capture accurate light fluence calculations in the clinical setting.

Real-time PDT Dose Dosimetry for Pleural Photodynamic Therapy.

PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), an eight-channel PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously from eight different sites in the pleural cavity during PDT. An isotropic detector with bifurcated fibers was used for each channel to ensure detected light was split equally to the photodiode and spectrometer. The light fluence rate distribution is monitored using an IR navigation system. The navigation system allows 2D light fluence mapping throughout the whole pleural cavity rather than just the selected points. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by applying optical properties correction and linear spectral fitting to the measured fluorescence data. The detection limit and the optical property correction factor of each channel were determined and validated using tissue-simulating phantoms with known varying concentration of Photofrin. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. The combination of 8-channel PDT dosimeter system and IR navigation system, which can calculate light fluence rate in the pleural cavity in real-time, providing a mean to determine the distribution of PDT dose on the entire pleural cavity to investigate the heterogeneity of PDT dose on the pleural cavity.

In vivo spectroscopic evaluation of human tissue optical properties and hemodynamics during HPPH-mediated photodynamic therapy of pleural malignancies.

Significance: Dosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose. Aim: Spectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies. Approach: Diffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC). Results: A total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] µM and [ 48,111 ] µM, for pre-PDT and post-PDT, respectively. Absorption coefficients, µa, ranged through [ 0.024 , 3.5 ] cm - 1 and [ 0.039 , 3 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, µs', ranged through [ 1.4 , 73.4 ] cm - 1 and [ 1.2 , 64 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Conclusions: There were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.

Cherenkov imaging for Total Skin Electron Therapy - an evaluation of dose uniformity.

Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat cancers on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high-energy electron beam and tissue. Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real-time using a time-gated intensified camera system. Each patient was monitored during TSET by in-vivo detectors (IVD) as well as Scintillators. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. A rigorous methodology for converting Cherenkov intensity to surface dose as products of correction factors, including camera vignette correction factor, incident radiation correction factor, and tissue optical properties correction factor. A comprehensive study has been carried out by inspecting various positions on the patients such as vertex, chest, perineum, shins, and foot relative to the umbilicus point (the prescription point).

A Comparison of Two Probes to Determine Rectum Optical Properties.

Tissue optical properties are crucial for determining the light dose delivered to the tumor. Two probes are compared: the two-catheter probe is based on transmittance measurement between one point source and one isotropic detector inside parallel catheters spaced at 0.5 cm along a 1-inch diameter transparent cylinder; and a 1-inch trans-rectal diffuse optical tomography (DOT) probe designed for prostate measurements, using a multiple fiber-array with source-detector separations of 1.4-10 mm. The two-catheter probe uses an empirical model for primary and scatter light fluence rates in the cylindrical cavity condition for anal PDT to determine optical properties along the source catheter using dual motors to move the source and detector along the catheters. The DOT probe uses finite element method (FEM) to obtain distribution of optical properties in 3D. Validations for the two probes were performed in liquid and solid phantoms. For each method, validation was performed in tissue-mimicking liquid phantoms for a range of known optical properties (µa between 0.05 and 0.9 cm-1 and µs' between 5.5 and 16.5 cm-1). To cross-check the two methods, solid phantoms were created of known optical properties at the University of Pennsylvania and sent for measurement to Princess Margaret Cancer Centre (PMH) to mimic realistic patient simulating conditions. Measurements were taken and optical properties were then recovered without knowing the expected values to cross-validate each probe. The results show modest agreement between the measured µa and µs'values, but high degree of agreement between the measured µeff performed independently using the two methods.

Infrared navigation system for light dosimetry during pleural photodynamic therapy.

Pleural photodynamic therapy (PDT) is performed intraoperatively for the treatment of microscopic disease in patients with malignant pleural mesothelioma. Accurate delivery of light dose is critical to PDT efficiency. As a standard of care, light fluence is delivered to the prescribed fluence using eight isotropic detectors in pre-determined discrete locations inside the pleural cavity that is filled with a dilute Intralipid solution. An optical infrared (IR) navigation system was used to monitor reflective passive markers on a modified and improved treatment delivery wand to track the position of the light source within the treatment cavity during light delivery. This information was used to calculate the light dose, incorporating a constant scattered light dose and using a dual correction method. Calculation methods were extensively compared for eight detector locations and seven patient case studies. The light fluence uniformity was also quantified by representing the unraveled three-dimensional geometry on a two-dimensional plane. Calculated light fluence at the end of treatment delivery was compared to measured values from isotropic detectors. Using a constant scattered dose for all detector locations along with a dual correction method, the difference between calculated and measured values for each detector was within 15%. Primary light dose alone does not fully account for the light delivered inside the cavity. This is useful in determining the light dose delivered to areas of the pleural cavity between detector locations, and can serve to improve treatment delivery with implementation in real-time in the surgical setting. We concluded that the standard deviation of light fluence uniformity for this method of pleural PDT is 10%.

Evaluation of Light Fluence Distribution Using an IR Navigation System for HPPH-mediated Pleural Photodynamic Therapy (pPDT).

Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcomes. However, current practice when delivering intrapleural PDT uses a point source to deliver light that is monitored by seven isotropic detectors placed within the pleural cavity to assess its uniformity. We have developed a real-time infrared (IR) tracking camera to follow the movement of the light point source and the surface contour of the treatment area. The calculated light fluence rates were matched with isotropic detectors using a two-correction factor method and an empirical model that includes both direct and scattered light components. Our clinical trial demonstrated that we can successfully implement the IR navigation system in 75% (15/20) of the patients. Data were successfully analyzed in 80% (12/15) patients because detector locations were not available for three patients. We conclude that it is feasible to use an IR camera-based system to track the motion of the light source during PDT and demonstrate its use to quantify the uniformity of light distribution, which deviated by a standard deviation of 18% from the prescribed light dose. The navigation system will fail when insufficient percentage of light source positions is obtained (<30%) during PDT.

A quality assurance program for clinical PDT.

Successful outcome of Photodynamic therapy (PDT) depends on accurate delivery of prescribed light dose. A quality assurance program is necessary to ensure that light dosimetry is correctly measured. We have instituted a QA program that include examination of long term calibration uncertainty of isotropic detectors for light fluence rate, power meter head intercomparison for laser power, stability of the light-emitting diode (LED) light source integrating sphere as a light fluence standard, laser output and calibration of in-vivo reflective fluorescence and absorption spectrometers. We examined the long term calibration uncertainty of isotropic detector sensitivity, defined as fluence rate per voltage. We calibrate the detector using the known calibrated light fluence rate of the LED light source built into an internally baffled 4″ integrating sphere. LED light sources were examined using a 1mm diameter isotropic detector calibrated in a collimated beam. Wavelengths varying from 632nm to 690nm were used. The internal LED method gives an overall calibration accuracy of ±4%. Intercomparison among power meters was performed to determine the consistency of laser power and light fluence rate measured among different power meters. Power and fluence readings were measured and compared among detectors. A comparison of power and fluence reading among several power heads shows long term consistency for power and light fluence rate calibration to within 3% regardless of wavelength. The standard LED light source is used to calibrate the transmission difference between different channels for the diffuse reflective absorption and fluorescence contact probe as well as isotropic detectors used in PDT dose dosimeter.

Light Fluence Dosimetry in Lung-simulating Cavities.

Accurate light dosimery is critical to ensure consistent outcome for pleural photodynamic therapy (pPDT). Ellipsoid shaped cavities with different sizes surrounded by turbid medium are used to simulate the intracavity lung geometry. An isotropic light source is introduced and surrounded by turbid media. Direct measurements of light fluence rate were compared to Monte Carlo simulated values on the surface of the cavities for various optical properties. The primary component of the light was determined by measurements performed in air in the same geometry. The scattered component was found by submerging the air-filled cavity in scattering media (Intralipid) and absorbent media (ink). The light source was located centrally with the azimuthal angle, but placed in two locations (vertically centered and 2 cm below the center) for measurements. Light fluence rate was measured using isotropic detectors placed at various angles on the ellipsoid surface. The measurements and simulations show that the scattered dose is uniform along the surface of the intracavity ellipsoid geometries in turbid media. One can express the light fluence rate empirically as ϕ =4S/As *Rd/(1 - Rd), where Rd is the diffuse reflectance, As is the surface area, and S is the source power. The measurements agree with this empirical formula to within an uncertainty of 10% for the range of optical properties studied. GPU voxel-based Monte-Carlo simulation is performed to compare with measured results. This empirical formula can be applied to arbitrary geometries, such as the pleural or intraperitoneal cavity.

Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy.

PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption µa (λ) and scattering µs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

A phase II trial of intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis and sarcomatosis.

PURPOSE: A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis. EXPERIMENTAL DESIGN: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete response, (b) failure-free survival time, and (c) overall survival time. Photosensitizer levels in tumor and normal tissues were measured. RESULTS: One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia. CONCLUSIONS: Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.

A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT.

Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. A dualcorrection algorithm is used to improve the agreement between calculations and in-situ measurements. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.

PDT dose dosimetry for Photofrin-mediated pleural photodynamic therapy (pPDT).

Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its photobleaching. The temporal integral of the product of in vivo photosensitizer concentration and light fluence is called PDT dose, which is an important dosimetry quantity for PDT. However, the detected photosensitizer fluorescence may be distorted by variations in the absorption and scattering of both excitation and fluorescence light in tissue. Therefore, correction of the measured fluorescence for distortion due to variable optical properties is required for absolute quantification of photosensitizer concentration. In this study, we have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and photosensitizer fluorescence data. We measured PDT dose at four sites in the pleural cavity during pleural PDT. We have determined an empirical optical property correction function using Monte Carlo simulations of fluorescence for a range of physiologically relevant tissue optical properties. Parameters of the optical property correction function for Photofrin fluorescence were determined experimentally using tissue-simulating phantoms. In vivo measurements of photosensitizer fluorescence showed negligible photobleaching of Photofrin during the PDT treatment, but large intra- and inter-patient heterogeneities of in vivo Photofrin concentration are observed. PDT doses delivered to 22 sites in the pleural cavity of 8 patients were different by 2.9 times intra-patient and 8.3 times inter-patient.

Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy.

The in vivo fluorescence emission from human prostates was measured before and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). A single side-firing optical fiber was used for both the delivery of 465 nm light-emitting diode excitation light and the collection of emitted fluorescence. It was placed interstitially within the prostate via a closed transparent plastic catheter. Fitting of the collected fluorescence emission spectra using the known fluorescence spectrum of 1 mg/kg MLu in an intralipid phantom yields a quantitative measure of the local MLu concentration. We found that an additional correction factor is needed to account for the reduction of the MLu fluorescence intensity measured in vivo due to strong optical absorption in the prostate. We have adopted an empirical correction formula given by C = (3.1 cm(-1)/micro's) exp (microeff x 0.97 cm), which ranges from approximately 3 to 16, with a mean of 9.3 +/-4.8. Using a computer-controlled step motor to move the probe incrementally along parallel tracks within the prostate we can determine one-dimensional profiles of the MLu concentration. The absolute MLu concentration and the shape of its distribution are confirmed by ex vivo assay and by diffuse absorption measurements, respectively. We find significant heterogeneity in photosensitizer concentration within and among five patients. These variations occur over large enough spatial scales compared with the sampling volume of the fluorescence emission that mapping the distribution in three dimensions is possible.

Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer.

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.

Phase II trial of pleural photodynamic therapy and surgery for patients with non-small-cell lung cancer with pleural spread.

PURPOSE: Non-small-cell lung cancer (NSCLC) with pleural spread is incurable, with median survival rates ranging from 6 to 9 months. Surgery alone fails to locally control this disease or extend survival beyond the accepted treatment, palliative chemotherapy. METHODS: We conducted a phase II trial to evaluate the effects on local control and survival of combining surgery with intraoperative photodynamic therapy (PDT), a light-based cancer treatment, in patients with NSCLC with pleural spread. Patients received porfimer sodium (2 mg/kg), 24 hours before surgery, at which time all gross tumor was resected and followed by illumination of the hemithorax with 630 nm light to a measured dose of 30 J/cm(2). Photosensitizer levels in tumor and surrounding normal tissue were measured. RESULTS: Twenty-two patients with NSCLC were enrolled; 17 underwent complete debulking and PDT, three underwent partial debulking/PDT, and two patients were unresectable. Local control of pleural disease at 6 months was achieved in 11 of 15 (73.3%; 95% CI, 44.9% to 92.2%) assessable patients. Median overall survival for all 22 patients was 21.7 months (95% CI, 17.7 to 25.8 months). Measured levels of porfimer sodium in tumor were greater than those measured in normal tissues, with ratios ranging from 1.19 to 22.42. CONCLUSION: Our results indicate surgery and PDT can be performed safely with very good local control. The median survival of 21.7 months, calculated from the time of surgery and PDT is encouraging. Further evaluation of this therapy is warranted.