Photodynamic Therapy in the Palliation of Late Stage Obstructing Non-Small Cell Lung Cancer* joseph LoCicero, Ill, M.D., F.C.C.P.; Mark Metzdorff, M.D.; and Carol Almgren, R.N.
Photodynamic therapy selectively destroys malignant tumors by laser activation of injected hematoporphyrin derivative. Between July 1985 and January 1989, ten patients underwent 13 courses of PDT for relief of endobronchial tumor obstruction due to endstage primary non-small lung cancer. Initial biopsy specimens demonstrated squamous carcinoma in eight patients and adenocarcinoma in two. At the time of treatment, all patients were considered surgically unresectable: T4N2M1(one), T4N2MO(one), T3N3Ml(two), T3N2MO(five), and T2N1MO(one). This latter patient had exclusionary medical conditions. The average Karnofsky status was 75 (worst was 60, best was 90). Obstruction was mainstem for six, bronchus intermedius in one, and left upper lobe in three. The average obstruction was 86±2 percent. Following treatment, the average obstruction was 57±3 percent. Responses were >50 percent
hotoactivation oflight-sensitive compounds to proPduce chemical reactions, a recognized phenomenon since 1900, has been applied to human cancer since 1966. 1 To date, an estimated 3,000 patients benefited from such treatment. 2 With the addition of fiberoptic delivery systems, physicians are treating tumors of virtually any organ system including the integument, central nervous system, aerodigestive tract, pulmonary, and genitourinary tract.3-9 Many of the articles on PDT for lung cancer deal with early stage disease. 11•1o- 12 One report by HughJones and Gardner 13 concentrates on those patients considered to have inoperable disease. Few, if any, reports address patient problems when PDT is an adjunct to other palliative modalities. Pass and colleagues 14 recently reported on a series of ten patients with late stage disease who exhibited improvement immediately following therapy. This report chronicles our long-term experience with PDT in patients who have advanced stage lung cancer undergoing additional treatment modalities. Particular attention is given to the quality of life for these terminally-ill patients. *From the Department of Surgery, Division of Cardiothoracic Surgery, Northwestern University Medical School, Chicago. Manuscript received September 11; revision accepted December 4. Reprint requests: Dr. LoCicero, Northwestern University Medical School, 303 East Chicago Avenue, 9-105, Chicago 6()611-3008
reduction in four and rm daily activities. The average Karnofsky status remrded at initial evaluation was 75. The worst Karnofsky status was 60 and the best 90. Six patients had no therapy prior to PDT, while four had prior therapeutic radiation to the primary tumor and mediastinum . One of these had also received preradiation chemotherapy. Patients most mmonly mmplained of rcent survive only three months, and one half are dead within six months. These patients with advanced disease have only a very short time to live and are miserable due to complications of their local-regional disease . Three of the six patients who received fi>llow-up radiation therapy had major complications. This is in contrast to the four pre-POT patients who had no radiation complications. Although this may he due to the extensive nature of the disease, there is the CHEST I 98 I 1 I JULY. 1990
99
potential that ionizing radiation therapy may also activate hematoporphyrin derivative, thus enhancing the side effects. This idea has been proposed by Kostron and associates21 after studying gamma radiation to a rat glioma model. Although this is highly unlikely, no experimental data exist to show one way or the other the effect of ionizing irradiation on HPD loaded tumors. We are studying currently in vitro several human lung cancer cell lines to evaluate this theory. Photodynamic therapy appears to offer palliation of the most significant problem for these patients (ie, endobronchial obstruction). In this series, all had symptomatic improvement and one half had decrease in tumor obstruction. The treatment, however, is not without significant consequences and potential complications. Although they may be mobile, sun exposure severely limits patients' activity for at least a month of their shortened life span. Patients with late stage lesions and their physicians must weigh this carefully when deciding among alternative therapies. Since the treatments can be performed as an outpatient with local anesthesia, there is less hospital time than with Nd:YAG therapy. Also, bleeding complications appear less frequent with PDT. No treatment in this group of patients is ideal and the decision for a particular therapy should remain individualized. REFERENCES I Wilson BC, Patterson MS. The physics of photodynamic therapy. Phys Med Bioll986; 31:327-60 2 Carruth JAS. Photodynamic therapy: state of the art. Lasers Surg Med 1986; 6:404-o7 3 Doiron OR, Keller GS. Porphyrin photodynamic therapy: principles and clinical applications. Curr Prob Dermatoll986; 15:8593 4 Gluckman JL, Warner M, Shymrick K, Peerless S. Photodynamic therapy: a viable alternative to conventional therapy for the upper aerodigestive tract? Arch Otolaryngol Head Neck
100
Surg 1986; ll2:949-52 5 Gluckman JL. Photodynamic therapy for early squamous cancer of the upper aerodigestive tract. Aust NZ J Surg 1986; 56:85357 6 McCaughan JS, Nims TA, Guy JT, Hicks WJ, Williams TE Jr, et al. Photodynamic therapy for esophageal tumors. Arch Surg 1989; 124:74-80 7 Herrera-Ornelas L, Petrelli NJ, Mittelman A, Dougherty TJ, Boyle DC. Photodynamic therapy in patients with colorectal cancer. Cancer 1986; 57: 677-84 8 Cortese DA. Bronchoscopic photodynamic therapy of early lung cancer. Chest 1986; 90:629-31 9 Benson RC Jr. Laser photodynamic therapy for bladder cancer. Mayo Clin Proc 1986; 61:859-64 10 Edell ES, Cortese DA. Bronchoscopic phototherapy with hematoporphyrin derivative for treatment oflocalized bronchogenic carcinoma: a 6ve-year experience. Mayo Clin Proc 1987; 62:814 II Hayata Y. Photoradiation. Chest 1986; 89(Suppl 4): 332 12 McCaughan JS Jr. Williams TE, Bethel BH. Photodynamic therapy of endobronchial tumors. Lasers Surg Med 1986; 6:33645 13 Hugh-Jones P, Gardner WN. Laser photodynamic therapy for non-operable bronchogenic squamous carcinoma. Q J Med 1987; 64:565-81 14 Pass HI, Delaney T, Smith PD, Bonner R, Russo A. Bronchoscopic phototherapy at comparable dose rates: early results. Ann Thorac Surg 1989; 47:693-99 15 American Joint Committee on Cancer: Manual for staging of cancer. Philadelphia: JB Lippincott Co, 1983: 99-105 16 HaraN, Ohta M, Tanaka K, Ichinose Y, Noge S, Miyazaki K. Assessment of the role of surgery for Stage III bronchogenic carcinoma. JSurg Oncoll984; 25:153-38 17 Mountain CF. The biologic operability of stage III non-small cell lung cancer. Ann Thorac Surg 1985; 40:6
Photodynamic therapy selectively destroys malignant tumors by laser activation of injected hematoporphyrin derivative. Between July 1985 and January 1989, ten patients underwent 13 courses of PDT for relief of endobronchial tumor obstruction due to endstage primary non-small lung cancer. Initial biopsy specimens demonstrated squamous carcinoma in eight patients and adenocarcinoma in two. At the time of treatment, all patients were considered surgically unresectable: T4N2M1(one), T4N2MO(one), T3N3Ml(two), T3N2MO(five), and T2N1MO(one). This latter patient had exclusionary medical conditions. The average Karnofsky status was 75 (worst was 60, best was 90). Obstruction was mainstem for six, bronchus intermedius in one, and left upper lobe in three. The average obstruction was 86±2 percent. Following treatment, the average obstruction was 57±3 percent. Responses were >50 percent
hotoactivation oflight-sensitive compounds to proPduce chemical reactions, a recognized phenomenon since 1900, has been applied to human cancer since 1966. 1 To date, an estimated 3,000 patients benefited from such treatment. 2 With the addition of fiberoptic delivery systems, physicians are treating tumors of virtually any organ system including the integument, central nervous system, aerodigestive tract, pulmonary, and genitourinary tract.3-9 Many of the articles on PDT for lung cancer deal with early stage disease. 11•1o- 12 One report by HughJones and Gardner 13 concentrates on those patients considered to have inoperable disease. Few, if any, reports address patient problems when PDT is an adjunct to other palliative modalities. Pass and colleagues 14 recently reported on a series of ten patients with late stage disease who exhibited improvement immediately following therapy. This report chronicles our long-term experience with PDT in patients who have advanced stage lung cancer undergoing additional treatment modalities. Particular attention is given to the quality of life for these terminally-ill patients. *From the Department of Surgery, Division of Cardiothoracic Surgery, Northwestern University Medical School, Chicago. Manuscript received September 11; revision accepted December 4. Reprint requests: Dr. LoCicero, Northwestern University Medical School, 303 East Chicago Avenue, 9-105, Chicago 6()611-3008
reduction in four and rm daily activities. The average Karnofsky status remrded at initial evaluation was 75. The worst Karnofsky status was 60 and the best 90. Six patients had no therapy prior to PDT, while four had prior therapeutic radiation to the primary tumor and mediastinum . One of these had also received preradiation chemotherapy. Patients most mmonly mmplained of rcent survive only three months, and one half are dead within six months. These patients with advanced disease have only a very short time to live and are miserable due to complications of their local-regional disease . Three of the six patients who received fi>llow-up radiation therapy had major complications. This is in contrast to the four pre-POT patients who had no radiation complications. Although this may he due to the extensive nature of the disease, there is the CHEST I 98 I 1 I JULY. 1990
99
potential that ionizing radiation therapy may also activate hematoporphyrin derivative, thus enhancing the side effects. This idea has been proposed by Kostron and associates21 after studying gamma radiation to a rat glioma model. Although this is highly unlikely, no experimental data exist to show one way or the other the effect of ionizing irradiation on HPD loaded tumors. We are studying currently in vitro several human lung cancer cell lines to evaluate this theory. Photodynamic therapy appears to offer palliation of the most significant problem for these patients (ie, endobronchial obstruction). In this series, all had symptomatic improvement and one half had decrease in tumor obstruction. The treatment, however, is not without significant consequences and potential complications. Although they may be mobile, sun exposure severely limits patients' activity for at least a month of their shortened life span. Patients with late stage lesions and their physicians must weigh this carefully when deciding among alternative therapies. Since the treatments can be performed as an outpatient with local anesthesia, there is less hospital time than with Nd:YAG therapy. Also, bleeding complications appear less frequent with PDT. No treatment in this group of patients is ideal and the decision for a particular therapy should remain individualized. REFERENCES I Wilson BC, Patterson MS. The physics of photodynamic therapy. Phys Med Bioll986; 31:327-60 2 Carruth JAS. Photodynamic therapy: state of the art. Lasers Surg Med 1986; 6:404-o7 3 Doiron OR, Keller GS. Porphyrin photodynamic therapy: principles and clinical applications. Curr Prob Dermatoll986; 15:8593 4 Gluckman JL, Warner M, Shymrick K, Peerless S. Photodynamic therapy: a viable alternative to conventional therapy for the upper aerodigestive tract? Arch Otolaryngol Head Neck
100
Surg 1986; ll2:949-52 5 Gluckman JL. Photodynamic therapy for early squamous cancer of the upper aerodigestive tract. Aust NZ J Surg 1986; 56:85357 6 McCaughan JS, Nims TA, Guy JT, Hicks WJ, Williams TE Jr, et al. Photodynamic therapy for esophageal tumors. Arch Surg 1989; 124:74-80 7 Herrera-Ornelas L, Petrelli NJ, Mittelman A, Dougherty TJ, Boyle DC. Photodynamic therapy in patients with colorectal cancer. Cancer 1986; 57: 677-84 8 Cortese DA. Bronchoscopic photodynamic therapy of early lung cancer. Chest 1986; 90:629-31 9 Benson RC Jr. Laser photodynamic therapy for bladder cancer. Mayo Clin Proc 1986; 61:859-64 10 Edell ES, Cortese DA. Bronchoscopic phototherapy with hematoporphyrin derivative for treatment oflocalized bronchogenic carcinoma: a 6ve-year experience. Mayo Clin Proc 1987; 62:814 II Hayata Y. Photoradiation. Chest 1986; 89(Suppl 4): 332 12 McCaughan JS Jr. Williams TE, Bethel BH. Photodynamic therapy of endobronchial tumors. Lasers Surg Med 1986; 6:33645 13 Hugh-Jones P, Gardner WN. Laser photodynamic therapy for non-operable bronchogenic squamous carcinoma. Q J Med 1987; 64:565-81 14 Pass HI, Delaney T, Smith PD, Bonner R, Russo A. Bronchoscopic phototherapy at comparable dose rates: early results. Ann Thorac Surg 1989; 47:693-99 15 American Joint Committee on Cancer: Manual for staging of cancer. Philadelphia: JB Lippincott Co, 1983: 99-105 16 HaraN, Ohta M, Tanaka K, Ichinose Y, Noge S, Miyazaki K. Assessment of the role of surgery for Stage III bronchogenic carcinoma. JSurg Oncoll984; 25:153-38 17 Mountain CF. The biologic operability of stage III non-small cell lung cancer. Ann Thorac Surg 1985; 40:6
