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Ann Thorac Surg 2004;78:388-389
© 2004 The Society of Thoracic Surgeons
Department of Radiation Oncology, Hospital of the University of Pennsylvania, 2 Donner, 3400 Spruce St, Philadelphia, PA 19104, USA
e-mail: hahn{at}xrt.upenn.edu
To the Editor:
The major differences between the phase I/II study reported by Schouwink and associates [1] and our study [2] are the maximally tolerated dose of photodynamic therapy (PDT) (longer drug-light interval), the nature of the dose-limiting toxicity, and the use of parenchymal-sparing surgical intervention in a substantial number of patients in our study. We agree with Drs Schouwink and Baas that the different maximally tolerated dose of Foscan-mediated PDT achieved in our study is likely the result of our treating patients with an intact lung. In a subset of mesothelioma patients treated at the maximally tolerated dose of Foscan and light, our group [3] found a pattern of cytokine release after light illumination that could explain the systemic inflammatory response observed in 2 patients in our study. Although, as Drs Schouwink and Baas point out, it is difficult to sort out the relative contributions of operation and PDT to the toxicities observed in these sorts of studies, we are fairly certain that the systemic inflammatory response observed in our study was the result of PDT.
The points raised by Drs Schouwink and Baas regarding light dosimetry are very important considerations in PDT. Improved light delivery and measurement techniques are needed to improve safety and enhance efficacy. Multichannel dosimetry systems using spherical detectors as pioneered by Drs Baas and Willem Star are an important first step in this direction. A different technique for light delivery was used in the majority of patients enrolled in our study. We used a laser fiber inserted in a modified endotracheal tube to deliver light to the thoracic cavity. This allowed greater flexibility in delivering light to the lung surfaces and diaphragmatic sulci. Another important difference was that we filled the hemithorax with a dilute intralipid solution for light dispersion, as reported by Pass and colleagues [4]. Not only does performance of a lung-sparing technique preclude the use of the "saline bag" technique for light dispersion reported by Schouwink and Baas, but we believe our technique also prevents the accumulation of blood that can occur outside the bag and results in the shielding of light from certain areas.
The differences in our two studies point to a real dilemma in the performance of clinical research, the balance between minimizing toxicities and enhancing efficacy. Performing an extrapleural pneumonectomy certainly facilitates the ease with which a gross total resection can be achieved, makes light delivery less demanding, and appears to allow delivery of a higher PDT dose, but the operation may be of prohibitive risk for certain patients who could otherwise tolerate a parenchymal-sparing procedure. Comparing our studies, it seems that the ability to offer more patients a procedure with fewer surgical complications and a lesser impact on quality of life comes at the cost of delivering a lower dose of PDT. With numbers too small to draw any definitive conclusions regarding the efficacy of the PDT component, this begs the question as to whether this is a reasonable compromise.
In the end, what this points to is the need to be flexible in our approach to patient care. For some patients, the risk-benefit ratio clearly supports the use of a parenchymal-sparing approach. In other patients, an extrapleural pneumonectomy may be the only option or may be more appropriate. Factors such as tumor volume (as discussed by Drs Schouwink and Baas) should be incorporated into the decision-making process. Furthermore, it might be reasonable to design a phase I study in which patients are stratified for PDT dose escalation on the basis of the surgical technique used.
References
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