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Ann Thorac Surg 2004;77:1021-1022
© 2004 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery,The University of Texas Medical Branch,301 University Boulevard,Galveston, TX 77551-0528, USA
e-mail: jzwische{at}utmb.edu
e-mail: rvertree{at}utmb.edu
The use of heat to treat disease has existed as long as recorded history. Observations relevant to cancer show heat does the following: (1) selectively kills cells as a function of thermal dose (duration of exposure x degree of temperature elevation); (2) selectively kills S-phase and radiation-resistant cells; (3) partially inhibits DNA repair; (4) kills cells with a defective heat-shock response; and (5) is a stimulus for apoptosis. Tumor cells, therefore, are more vulnerable to heat than normal cells. The clinical application of hyperthermia, often in conjunction with chemotherapeutic agents, includes three general methods based on the extent of the body treated. Localized hyperthermia utilizes heat for primary and recurrent tumors and appears most successful for head and neck tumors. Regional or isolated organ/limb hyperthermia utilizes heat restricted to specific regions of the body. Response has been documented in select patients for tumors of the limbs, liver, pancreas, esophagus, gastrointestinal tract, colon, and rectum. Whole-body hyperthermia uses methods that heat the entire body to a target core temperature of approximately 42 degrees centigrade to treat metastatic disease. Effectiveness is still controversial because of the difficulty in administering and monitoring systemic hyperthermia and limited experience.
The accompanying article by Shigemura et al is the latest from a group with extensive experience in the therapeutic application of hyperthermia. The combination of surgical resection of the primary lesion and pleural perfusion thermochemotherapy using video-assisted thoracoscopic surgery (VATS) addresses the large number of patients with locally advanced lung cancer. While heating the pleural space with an extracorporeal circuit for up to two hours, no serious clinical complications occurred, and when used in conjunction with maximal surgical debulking for locally advanced lung cancer, patients realized a presumed survival benefit. As with most early reports, the apparent success of the treatment may be misleading because the selected patients were of different stages, pathology, and treatment regimens. The statistic of median survival time in this application, when so few of the patients died (3/17), actually understates the "typical" survival. This communication should simply report that 77% of the patients survived the 12-month study. The study was not prospective, randomized, or controlled; however, the basic message is important because hyperthermia has potential as a physiologic tool in manipulating the therapeutic response of cancer.
We are encouraged by the results of this Phase I trial, which show that patients with locally advanced lung cancer can safely withstand high thermal doses and concentrations of platinum-based chemotherapy when administered by pleural perfusion. Prospective randomized, controlled, multicenter trials need to be conducted to determine the risk/benefit of this new treatment approach. To allow these trials to proceed, the hyperthermic technique, patient selection criteria, chemo and/or radiation modality, as well as the technique for surgical resection of local tumors, must be established.
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