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Photoradiation Therapy for Bronchogenic Cancer

1982; Elsevier BV; Volume: 81; Issue: 3 Linguagem: Inglês

10.1378/chest.81.3.265

1931-3543

Thomas J. Dougherty,

Nonmelanoma Skin Cancer Studies

Photoradiation therapy (PRT) was introduced into clinical studies of malignant tumors in 1978 and 1979 by Dougherty and colleagues.1Dougherty TJ Kaufman JE Goldfarb A Weishaupt KR Boyle DG Mittelman A. Photoradiation therapy for the treatment of malignant tumors..Cancer Res. 1978; 38: 2628-2635PubMed Google Scholar,2Dougherty TJ Lawrence G Kaufman J Boyle DG Weishaupt KR Goldfarb A. Photoradiation in the treatment of recurrent breast carcinoma..J Natl Cancer Inst. 1979; 62: 231-237PubMed Google Scholar These initial studies related primarily to treatment of cutaneous and subcutaneous lesions. Subsequent studies, including treatment of several types of tumors not previously treated, were reported by Forbes.3Forbes IJ Cowled PA Leong ASY et al.Phototherapy of human tumors using hematoporphyrin derivative..Med J Aust. 1980; 2: 489-493PubMed Google Scholar The application of PRT to more remote lesions by means of laser-fiberoptic light-delivery systems was described in 19814Dougherty TJ Thoma RE Boyle DG Weishaupt KR. Interstitial photoradiation therapy for primary solid tumors in pet cats and dogs..Cancer Res. 1981; 41: 401-404PubMed Google Scholar and at a recent Workshop on PRT.5Workshop on Porphyrin Photosensitization, Sept 28-29, 1981. Washington, DC: Plenum Press (in press)Google Scholar This new approach to cancer therapy utilizes hematoporphyrin derivative (Hpd) as a systemically applied photosensitizer of tumors and visible light (usually near 630 nm) as the photoactivating source. Its therapeutic ratio and efficacy depend on the ability of Hpd to be retained longer in malignant tissues than in many normal tissues and its efficient phototoxicity.6Bugelski PJ, Porter CW, Dougherty TJ. Autoradiographic distribution of hematoporphyrin derivative in normal and tumor issue of the mouse. (in press)Google Scholar The application of PRT to life-threatening tumors is just beginning but is showing promise in treatment of the bronchus, trachea, esophagus, bladder, and brain.3Forbes IJ Cowled PA Leong ASY et al.Phototherapy of human tumors using hematoporphyrin derivative..Med J Aust. 1980; 2: 489-493PubMed Google Scholar,5Workshop on Porphyrin Photosensitization, Sept 28-29, 1981. Washington, DC: Plenum Press (in press)Google Scholar In this issue of Chest appears the first report of the use of PRT for the treatment of tumors of the tracheobronchial tree (see page 269). Hayata and colleagues have demonstrated that both late and early lesions, including all the major histologic types, are responsive to PRT. Patients were injected with 2.5 to 4.0 mg/kg of Hpd, and two days later the activating light was delivered endoscopically to the tumors via a single quartz fiberoptic threaded through the biopsy channel of the bronchoscope. The light source was an argon laser-dye laser system utilizing rhodamine B dye and emitting near 630 nm. Such systems are capable of delivering several watts of power to a tumor site if necessary through single or multiple fibers. Although this report describes endoscopic PRT treatment by directing the light to the surface of the lesions, this group and others also have applied the light interstitially by inserting the fiber into the lesions to reach remote areas (ie, deeper than 1.5 to 2.0 cm). The results of this study by Hayata and his colleagues are significant for several reasons despite the early nature of the work. Others, aware of Hayata's earlier studies, have been able to obtain results very similar to his in applying PRT to bronchial and other tumors.9Kinsey JH Cortese DA Sanderson DR. Detection of hematoporphyrin fluorescence during fiber-optic bronchoscopy to localize early bronchogenic carcinoma..Mayo Clin Proc. 1978; 53: 594-600PubMed Google Scholar The ability to relieve obstructions by tumors in the trachea and bronchus within as little as one day posttreatment allows this method to be considered for palliative purposes in certain patients. Many patients, at this stage, are not surgical candidates and, further, may not be amenable to radiation therapy. Provided the light-delivery fiber can reach the obstruction, such patients can be treated with PRT. However, there are potential complications to be considered. The immediate reaction to PRT is usually edema, which can result in temporary but possibly increased obstruction. Also, as Hayata points out, frequently there is seen a rapid build-up of heavy sputum, which can contribute to further obstruction. Hemoptysis is also a possibility in advanced patients following PRT. While not seen by Hayata and his colleagues, a few cases have been reported by others.5Workshop on Porphyrin Photosensitization, Sept 28-29, 1981. Washington, DC: Plenum Press (in press)Google Scholar This is generally seen one to two weeks following treatment. While hemoptysis is a common problem in patients with advanced lung tumors, rapid necrosis of large lesions, as a result of PRT, apparently can induce this situation. It is possible that patients at risk in this way can be excluded from PRT treatment. In spite of these complications, in advanced cases, relief of dyspnea and obstructive phenomena can be obtained to the benefit of the appropriate patient. A significant group of patients described by Hayata et al are those who were not surgical candidates before PRT but became candidates for potentially curative surgery after PRT. Thus, for example, resection could become possible in patients with tumor invading the trachea or carina if these tumors are eradicated by PRT, as has been demonstrated in several cases here. Perhaps the most promising results are those obtained in the early cases. Complete response for nearly 1½ years has been seen in a patient treated by PRT for early squamous cell carcinoma recognized initially by sputum cytology. Further, carcinoma in situ and severe metaplasia also retain Hpd. As shown by Hayata and others,5Workshop on Porphyrin Photosensitization, Sept 28-29, 1981. Washington, DC: Plenum Press (in press)Google Scholar such lesions can be eradicated by PRT with very little trauma and few side effects. The challenge, of course, is to find such patients. Earlier reports have demonstrated the use of Hpd fluorescence to localize early tumors of the bronchus.7Doiron DR Profio AE Vincent RG Dougherty TJ. Fluorescence bronchoscopy for detection of lung cancer..Chest. 1979; 76: 27-32Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 8Profio AE Doiron DR King EG. Laser fluorescence bronchoscope for localization of occult lung tumors..Med Phys. 1979; 6: 523-525Crossref PubMed Scopus (80) Google Scholar, 9Kinsey JH Cortese DA Sanderson DR. Detection of hematoporphyrin fluorescence during fiber-optic bronchoscopy to localize early bronchogenic carcinoma..Mayo Clin Proc. 1978; 53: 594-600PubMed Google Scholar The combination of early localization by Hpd fluorescence and early eradication by PRT of both frank carcinoma and cases of severe metaplasia is potentially of considerable significance. In addition, the fluorescence can be helpful in identifying areas of tumor invasion even in patients with evident tumor in other areas. Many questions regarding PRT remain to be answered, especially regarding long-term clinical results and technical questions related to light dosimetry and the possible contribution of heat during treatment to the overall effects. The interest of groups of clinicians, physicists, engineers, and chemists in these problems provides the hope that the answers will not be much longer in coming. *Considerable advances in Hpd preparation and in light-delivery systems have already been made. Interested investigators may contact Oncology Research and Development, Inc., 3348 Genesee Street, Cheektowaga, NY 14225 for details. *Considerable advances in Hpd preparation and in light-delivery systems have already been made. Interested investigators may contact Oncology Research and Development, Inc., 3348 Genesee Street, Cheektowaga, NY 14225 for details.