Lhermitte sign and myelopathy after irradiation of the cervical spinal cord in radiotherapy treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The goal of this work was to examine toxicity and risk factors after irradiation of the cervical spinal cord. PATIENTS AND METHODS: A total of 437 patients irradiated for a laryngeal and oropharyngeal carcinoma were eligible (median follow-up 27 months). Spinal cord contouring was defined differently over time as anatomically defined spinal cord area (SCA) and the spinal cord on CT (SC) with a margin of 3 or 5 mm (SCP3/SCP5). RESULTS: None developed chronic progressive radiation myelopathy (CPRM) (maximum spinal dose 21.8-69 Gy); 3.9% (17/437) developed a Lhermitte sign (LS) with a median duration of 6 months (range 1-30 months) and was reversible in all patients. Risk factors for developing LS were younger age (52 vs. 61 years, p < 0.001), accelerated RT (12/17 patients, p < 0.005), and dose-volume relationships for SCA with ≥ 45 Gy of 14.15 cm(3) and 7.9 cm(3) for patients with and without LS, respectively. CONCLUSION: LS is more frequently observed in younger patients and in patients treated with accelerated radiotherapy. A dose-volume relationship was seen for V45 in the case of SCA. For higher doses, no clear dose-volume relationships were observed.

Manual calculation of treatment time for high dose rate brachytherapy with a flexible intraoperative template (FIT).

A method is presented for estimating the total treatment time for a brachytherapy radiation fraction with a planar flexible intraoperative template (FIT), using an 192Ir high dose rate afterloading device. The FIT can be rectangular or irregularly shaped. The manual calculation serves as an independent check of the treatment time calculated by the treatment planning system for applications with varying sizes, shapes and dose prescription depths. The parameters required for the calculation are the number of active dwell positions, the catheter spacing and dwell position spacing, the source strength, the applied dose and the depth of dose prescription. For a fixed depth of dose prescription (1.25 cm) and fixed dwell position and catheter spacing (0.5 and 1 cm respectively) the manual calculation accurately predicts (usually within 2%) the total treatment time as calculated by the treatment planning system. For varying catheter and dwell position spacings and dose prescription depths the accuracy is still within 7%. An action threshold of 5% allows detection of errors made in the number of active dwell positions (+/-9), catheter spacing (+/-1 mm) and dose prescription depth (+/-1 mm). Errors in dwell position spacing (0.25 cm or more) could also be accurately detected.

A CT-assisted method of dosimetry in brachytherapy of lung cancer. Rotterdam Oncological Thoracic Study Group.

BACKGROUND: The toxicity of endobronchial brachytherapy (EB), in particular fatal haemoptysis and bronchial wall necrosis, has been correlated with the total dose, fraction size, volume encompassed by the 100% isodose, and a proximal tumor location. We describe a CT-based planning method which, by improving target volume definition and volumetric dose information, can improve the therapeutic ratio of EB. MATERIALS AND METHODS: Sixteen CT-assisted EB procedures were performed in patients who were treated with palliative high-dose rate EB. The CT data were used to analyze applicator position in relation to anatomy. An example of a three-dimensional optimized treatment plan was generated and analyzed using different types of dose-volume histograms. RESULTS: The procedure was well tolerated by patients and no post-procedure complications were observed. The bronchial applicator was eccentrically positioned at the level of the carina/mainstem bronchus in 12 (of 14) CT scans. A planning CT prior to EB was not found to be useful as the final target volume and/or the final applicator position were not reliably predicted before the therapeutic bronchoscopy. CT-scans performed with the applicator in situ allowed the bronchial segments in the target volume to be identified and enabled dose prescription to the bronchial mucosa. CONCLUSIONS: CT-assisted EB is feasible and underlines the need for using centered applicators for proximally located tumors. By enabling accurate mucosal dose prescription, CT-assisted EB may reduce the toxicity of fractionated EB in the curative setting. However, faster on-line EB treatment planning is needed for the routine clinical application of this technique.

Comparison between isotropic and nonisotropic dosimetry systems during intraperitoneal photodynamic therapy.

BACKGROUND AND OBJECTIVE: On-line monitoring of light fluence during intraperitoneal photodynamic therapy (IP PDT) is crucial for safe light delivery. A flat photodiode-based dosimetry system is compared with an isotropic detector-based system in patients undergoing IP PDT. STUDY DESIGN/MATERIALS AND METHODS: Flat photodiodes and spherical detectors were placed side by side in the abdomen, for simultaneous light dosimetry in 19 patients. Tissue phantom experiments were performed to provide a preliminary estimate of the tissue optical properties of the peritoneum. RESULTS: The conversion factor between systems for 630-nm light was found to be 1.7 +/- 0.12. The mu(eff) of the tissues in the abdomen is estimated to vary between 0.5 cm(-1) to 1.4 cm(-1) assuming a mu(s)' = 7 cm(-1). CONCLUSIONS: The measured conversion factor should allow for comparison of light fluences with future clinical protocols that use an isotropic-based detector system. Differences in the optical properties of the underlying tissues may contribute to the variability in light measurements.

Mucosal dose prescription in endobronchial brachytherapy: a study based on CT-dosimetry.

PURPOSE: To investigate the consequences of using different dose prescription methods for endobronchial brachytherapy (EB), both with and without the use of a centered applicator. MATERIALS AND METHODS: A CT scan was performed during EB procedures in 13 patients after insertion of the lung applicator. A dosimetric analysis was subsequently performed in five of these patients using a 3D-brachytherapy treatment planning system (PLATO v13.3, Nucletron). RESULTS: Dose prescription to the mucosa yields uniform dose distributions to the bronchial mucosa when a centrally positioned applicator is used. When non-centrally positioned applicators are used, mucosal dosing results in a significant underdosage to parts of the target volume. Due to the rapid dose fall-off in EB, dose prescription to the mucosa resulted in inadequate coverage of the outer portion of the bronchial wall and adjacent peribronchial space. When compared to mucosal dose prescription, prescription to the outer aspect of the bronchial wall appears to improve target coverage while limiting the hyperdose (i.e., 200%) volume. The diameters of the different bronchial segments, as determined by CT measurements in 13 patients, correlated well with calculated values based upon the tracheal diameter. CONCLUSIONS: Mucosal dose prescription should only be used in combination with centered EB applicators. Given the rapid dose fall-off in EB mucosal dose prescription should be used with caution in curative treatments where EB, without additional external radiotherapy, is used as the sole treatment modality. In curative EB, both improved target coverage and a limited hyperdose volume can be achieved by dose prescription to the outer aspect of the bronchial wall.

Short- and long-term normal tissue damage with photodynamic therapy in pig trachea: a fluence-response pilot study comparing Photofrin and mTHPC.

The damage to normal pig bronchial mucosa caused by photodynamic therapy (PDT) using mTHPC and Photofrin as photosensitizers was evaluated. An endobronchial applicator was used to deliver the light with a linear diffuser and to measure the light fluence in situ. The applied fluences were varied, based on existing clinical protocols. A fluence finding experiment with short-term (1-2 days) response as an end point showed considerable damage to the mucosa with the use of Photofrin (fluences 50-275 J cm(-2), drug dose 2 mg kg(-1)) with oedema and blood vessel damage as most important features. In the short-term mTHPC experiment the damage found was slight (fluences 12.5-50 J cm(-2), drug dose 0.15 mg kg(-1)). For both sensitizers, atrophy and acute inflammation of the epithelium and the submucosal glands was observed. The damage was confined to the mucosa and submucosa leaving the cartilage intact. A long-term response experiment showed that fluences of 50 J cm(-2) for mTHPC and 65 J cm(-2) for Photofrin-treated animals caused damage that recovered within 14 days, with sporadic slight fibrosis and occasional inflammation of the submucosal glands. Limited data on the pharmacokinetics of mTHPC show that drug levels in the trachea are similar at 6 and 20 days post injection, indicating a broad time window for treatment. The importance of in situ light dosimetry was stressed by the inter-animal variations in fluence rate for comparable illumination conditions.

Monte Carlo simulations for EndoBronchial Photodynamic Therapy: the influence of variations in optical and geometrical properties and of realistic and eccentric light sources.

BACKGROUND AND OBJECTIVE: Light dosimetry for endobronchial photodynamic therapy is not very advanced to date. This study investigates the dependency of the fluence rate distribution in the bronchial wall on several parameters. STUDY DESIGN/MATERIALS AND METHODS: A Monte Carlo model is employed for the illumination of a cylindrical cavity by a linear diffuser to compute the fluence rate distribution in the tissue. The influence of optical and geometrical properties (e.g., the absorption coefficient of the bronchial mucosa and the diameter of the treated lumen) have been investigated, as well as the consequences of varying output characteristics of the diffusers. The optical properties used are those of ex vivo pig bronchial mucosa. RESULTS: With on-axis linear diffusers that can be modelled as a row of isotropic point sources, a constant fluence rate buildup factor can be employed for varying diffuser lengths and lumen diameters. Extreme off-axis placement of the diffuser causes a highly variable, considerable increase in the maximum fluence rate as well as a highly asymmetrical fluence rate profile on the circumference of the illuminated lumen. The fluence rate profiles resulting from illumination with realistic diffusers can be evaluated by implementing the measured radiance profiles of these diffusers in the model. The changes in fluence rate caused by variations in the optical properties of the bronchial mucosa could be accounted for by diffusion theory. This relationship can be used to extrapolate the ex vivo results to the clinical situation. CONCLUSION: A set of practical rules of thumb is presented that can help to estimate fluence rate distributions in clinical practice.

Improvements in the design of linear diffusers for photodynamic therapy.

The angular radiance distribution of several linear diffusers used for photodynamic therapy (PDT) was measured. The forward scattering found previously was not observed for these designs. The improved isotropy leads to a better agreement between intended treatment site and actual maximum of the fluence rate profile when the linear diffuser is used in a hollow, cylindrical organ.

Applicator for light delivery and in situ light dosimetry during endobronchial photodynamic therapy: First measurements in humans.

This paper presents a design of an applicator for light delivery and light dosimetry during endobronchial photodynamic therapy (EB-PDT). The design incorporates a linear diffuser that is fixed in the centre of the lumen by a steel spring basket that does not block air flow. An isotropic light detector is included in this design, to measure the light fluence actually delivered to the bronchial mucosa surface. The applicator is designed for use with common bronchoscopy equipment, and can be used with bronchoscopes with a large biopsy channel ( approximately 3 mm). The first clinical measurements were performed and caused no additional discomfort to the (nonphotosensitized) patients. The data showed considerable inter-patient variability of the light fluence rate measured as a result of fixed output power of the diffuser. This fact and the expected strong dependence of the fluence rate on the lumen diameter stress the importance of in situ fluence rate measurement for a proper evaluation of the relationship between light fluence and the biological response of EB-PDT.

Light distribution by linear diffusing sources for photodynamic therapy.

The distribution of the light emitted by linear light diffusers commonly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser.

Ex vivo light dosimetry and Monte Carlo simulations for endobronchial photodynamic therapy.

The light distribution during photodynamic therapy of the bronchial tree has been estimated by measuring the fluence rate in ex vivo experiments on dissected pig bronchi. The trachea was illuminated (630 nm) with a cylindrical diffuser and the fluence rate was measured with a fibre optic isotropic probe. The experiment with the diffuser on the central axis was also simulated with Monte Carlo techniques using the optical properties that were determined with a double-integrating-sphere set-up. The results from ex vivo experiments and the Monte Carlo simulations were found to agree within the error of measurement (15%), indicating that the Monte Carlo technique can be used to estimate the light distribution for varying geometries and optical properties. The results showed that the light fluence rate in the mucosa of the tracheal tract may increase by a factor of six compared to the fluence rate in air (in the absence of tissue). This is due to the scattering properties of the tissue and the multiple reflections within the cavity. Further ex vivo experiments showed that the positioning of the diffuser is critical for the fluence rate in the lesion to be treated. When the position of the diffuser was changed from the central axis to near the lesion, the fluence rate in the mucosa increased significantly by several orders of magnitude as compared to the initial (central) illumination. The inter- and intraspecimen variations in this increase were large (+/- 35%) because of variations in optical and geometrical properties and light source positioning, respectively. These variations might cause under- or overdosage resulting in either insufficient tumour necrosis or excessive normal tissue damage.