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Objective: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung., Material and Methods: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT., Results: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116)., Conclusion: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and "rheumatoid-like" nodules. Two months after the administration of combined-modality therapy for stage IIIA non-small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.

Photodynamic therapy has been used since 1980 at our institution for the management of cancer of the tracheobronchial tree. We identified 13 patients (14 cancers) who were thought to be surgical candidates but who elected to have photodynamic therapy. Thirteen cancers (93 percent) had a complete response to hematoporphyrin-derivative phototherapy. Ten cancers (71 percent) showed a complete response after single treatment, and three (21 percent) required a second course of therapy to achieve a complete response. Ten (77 percent) of 13 cancers have shown no local recurrence. Three patients with persistent cancer underwent surgical resection and were found not to have nodal involvement. We concluded that photodynamic therapy is an alternative to surgical resection in the management of early superficial squamous cell carcinoma.

Hematoporphyrin derivative phototherapy (HpD-PT) has been successfully used to localize and treat superficial squamous cell cancers. Bleomycin sulfate is a glycopeptide antibiotic that has antineoplastic properties against squamous cell cancers. Because both HpD-PT and bleomycin chemotherapy are accepted forms of treatment for squamous cell cancer and their cytotoxicity is mediated by singlet oxygen and oxygen radicals, we studied the possibility of enhancing the response of solid tumors to HpD-PT by combining this modality with systemic bleomycin chemotherapy in a murine tumor model. Bleomycin did not enhance HpD-PT significantly. Also, we are not confident that HpD-PT alone or in combination with other agents can eradicate solid tumors; it certainly did not in this syngeneic murine tumor model.

In this paper the potential use of hematoporphyrin-derivative (HpD) phototherapy in the local treatment of bronchogenic carcinoma is discussed. Ten patients with cancer involving the tracheobronchial tree have completed at least one course of HpD-mediated laser phototherapy administered by means of the flexible fiberbronchoscope. Complete response was obtained in four cases, and in each case the tumor was small and superficial. Larger tumors with greater degrees of invasion showed only a partial response. Two patients with tumors eroding through the bronchial wall died following treatment. It appears that HpD phototherapy may be useful for control of only small, superficial squamous cell carcinomas of the tracheobronchial tree and only those within the range of the flexible fiberbronchoscope.

Between December 1980 and April 1986 at our institution, 38 patients with cancer that involved the tracheobronchial tree (a total of 40 carcinomas) completed at least one course of hematoporphyrin derivative phototherapy. A complete response occurred in 13 patients (with 14 carcinomas). Eleven of these carcinomas did not recur during follow-up periods that ranged from 3 to 53 months. Three carcinomas recurred at 9, 12, and 35 months, respectively. For 26 carcinomas, the response was less than complete, and alternative therapy was necessary. The carcinomas in patients with a complete response were radiographically occult, were less than 3 cm2 in surface area, and appeared superficial at bronchoscopy. Our experience supports the use of hematoporphyrin derivative phototherapy as an alternative to surgical resection in carefully selected patients.

Hematoporphyrin derivative used in conjunction with the Mayo Clinic bronchofiberscopic fluorescence detection system allows accurate localization of radiographically occult early squamous cell carcinoma. Thirteen tumors were localized in 10 patients with radiographically occult lung cancer. Six were in situ with or without microinvasion and were also bronchoscopically occult. Localization of these 6 tumors was expedited by the use of hematoporphyrin derivative and the bronchoscopic fluorescence detection system. Hematoporphyrin-derivative fluorescence was not specific for carcinoma and was also detected in areas of moderate and marked squamous cellular atypia. Thus, although detection of hematoporphyrin-derivative fluorescence suggests the presence of cancer, proof depends on histologic or cytologic confirmation.

Bronchoscopic phototherapy is available now for 2 distinct categories of tracheobronchial cancer: roentgenographically occult superficial squamous cell carcinoma and advanced malignancy causing significant airway obstruction. Laboratory and clinical experience show that the photodynamic effect of hematoporphyrin derivative phototherapy (HpD-PT) may be useful for treating superficial cancers that penetrate less than 5 mm into bronchial mucosa. The larger, obstructing cancers are better managed by high-power laser sources, such as the YAG laser, which are effective by hyperthermal photocoagulation, thermal necrosis, and tissue vaporization.

During the past 10 years, 54 patients, all men, were found to have roentgenographically occult lung cancer. The mean age was 61 years (range 45 to 76 years). All patients had abnormal findings on sputum cytologic study (carcinoma in 41 patients and squamous cell atypia in 13). The cancer was localized by bronchoscopy in all patients (range one to five examinations, mean 1.5). Seventy-five percent of the tumors were localized within 169 days of the abnormal sputum cytologic examination. Pulmonary resection for cure was performed in all patients: lobectomy in 38, pneumonectomy in nine, and bilobectomy in seven. Operative mortality was 5.6% (three patients). Fifty-eight cancers were resected, all squamous cell carcinomas (two had a component of large cell cancer). Tumor TNM classification (AJC) was TIS N0 M0 in 19 patients, T1 N0 M0 in 25, T1 N1 M0 in five, T2 N1 M0 in four, and T3 N0 M0 in one. Overall 5 year actuarial survival rate (lung cancer deaths only) was 90%. Five-year survival rate for the 44 patients with TIS N0 M0 and T1 N0 M0 neoplasms was 91%. Currently, 21 patients have died, but only 10 of lung cancer. Subsequent additional lung cancer developed in 12 patients (22%). Eleven of these patients had a second primary squamous lung cancer, six of which again were occult. We conclude that patients with occult lung cancer have a strong likelihood of long-term survival if treated early. Close surveillance is indicated because of the high incidence of a second primary lung cancer.

Phototherapy in the presence of hematoporphyrin (HPD) produces cytotoxicity through both energy- and power-dependent mechanisms. The resulting cellular death demonstrates the promise of HPD in the therapy of small cancers. This article reports our clinical experience and follow-up results of treating 19 patients with cancer of the tracheobronchial tree, who have completed at least one course of HPD administered via the flexible fiberoptic bronchoscope.

In recent years hematoporphyrin derivative (HpD), a mixture of porphyrin compounds that have an increased affinity for malignant tissue, has been used as an endobronchial tumor indicator to facilitate the bronchoscopic localization of early squamous cell carcinoma of the central tracheobronchial tree. In this article the authors describe four different bronchoscopic fluorescence detection systems that have facilitated the bronchoscopic localization of HpD-labeled early squamous cell carcinoma of the trachea and central bronchi.

Between January 1983 and October 1985, 65 patients with malignant airway compromise have had 93 flexible bronchoscopic placements of a nylon afterloading catheter for low dose rate iridium-192 temporary intraluminal brachytherapy. All patients received prior (59 patients) and/or concurrent (13 patients) external beam irradiation to "tolerance" and were not candidates for surgery. Forty of these patients also received neodymium-YAG laser treatment prior to brachytherapy in a planned combined approach to provide immediate symptomatic relief and facilitate catheter placement. A dose of 3,000 cGy is prescribed to 5 mm and 10 mm radii over 20-40 hours in the bronchus and trachea, respectively. Of 59 patients treated with palliative intent, 40 patients (68 percent) have had follow-up bronchoscopy, 18 patients have had clinical follow-up only, and one patient was lost to follow-up. Of 40 patients examined by bronchoscope in follow-up, 24 (60 percent) responded, eight were stable, and eight progressed. Lack of progression after prior external beam radiation for periods of greater than 12 months, six-12 months and less than six months yielded response rates to brachytherapy in 83 percent, 50 percent and 31 percent, respectively. Most patients with clinical follow-up only expired at early intervals with airway palliation from extra-airway disease progression. Four of five patients treated with curative intent are disease-free at a median of 16 months. Eleven patients have experienced fistula and/or hemorrhage, of which seven instances (11 percent of all patients) appear to be treatment-induced. This brachytherapy technique is simple, well tolerated, and convenient for the patient providing airway palliation in the significant majority of patients with acceptable risk.

Hematoporphyrin is preferentially concentrated by cancer tissue and therefore is a potentially useful chemical marker. This report demonstrates the effectiveness of a photoelectric hematoporphyrin fluorescence detector used simultaneously with flexible fiberoptic bronchoscopy as a means of detecting and localizing bronchogenic carcinoma. The detector generates an audio signal when fluorescence is within the visual field of the bronchoscope. Of interest is that an audio signal was generated which indicated hematoporphyrin fluorescence in areas where no mucosal abnormality had been seen. These areas proved to be carcinoma in situ.

The flexible fiberoptic bronchoscope is currently the standard tool for localization of radiographically occult carcinomas of the tracheobronchial tree. It allows direct inspection of proximal airways and can establish the location of most occult lung cancers. A small percentage of patients present with bronchoscopically as well as radiographically occult carcinoma, particularly challenging because definitive localizations is required before a therapeutic plan can be outlined. Selective cytologic brushing of each lobar segment, taking random biopsy specimens, has been used to assist in localization of these early cancers. Recently, fluorescent compounds have been used to assist in localizing early lung cancers and in the treatment of radiographically occult carcinoma. We review the current methods of bronchoscopic localization and treatment of radiographically occult lung cancer.