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Lung Cancer Alliance

Abbreviations: AF = autofluorescence bronchoscopy: LDSCT = low-dose spiral CT

It has been argued that chest radiography and sputum cytology are not adequately sensitive for the detection of early lung cancer. (1) Central squamous cell lung cancers are only infrequently detected in low-dose spiral CT (LDSCT) screening studies, (2-4) even when cytology is added to the screening protocol. The introduction of autofluorescence bronchoscopy (AF) highlighted the ability to directly visualize central squamous carcinoma in patients who are at high risk for lung cancer. In a meta-analysis of > 1,000 cases, the sensitivity of AV combined with conventional white light bronchoscopy for detection of preinvasive epithelial neoplasms was 80%. (5) We hypothesized that AF combined with low-dose spiral CT (LDSCT) of the chest might be useful a screening strategy for a cohort of high-risk patients.

As a part of an ongoing prospective clinical trial of lung cancer screening, high-risk patients were offered bimodality screening (AF and LDSCT) if they had two or more of the following risk factors: (1) history of tobacco use > 20 pack-years in density, (2) history of previously treated aerodigestive tract malignancy with no evidence of disease for > 2 years, (3) asbestos related lung disease documented by chest radiography, or (4) COPD with a measured FE[V.sub.1] of < 70% predicted. All subjects underwent chest radiography, LDSCT of the chest without contrast, sputum for cytology, and AF in a single outpatient visit when possible. The end point of the trial is the detection of lung cancer. Of a projected total accrual goal of 208 patients, 121 patients have completed testing. This report summarizes the results from the first 100 patients. Accrual to this trial is ongoing.

Ninety-nine percent of the patients were current or former smokers (median age, 63 years). Forty-five percent had evidence of asbestos-related lung disease, 58% had moderate COPD, and 30% had a history of previous cancer. To date, eight intrathoracic cancers (8%) [Table 1] and two cases of laryngeal carcinoma in situ have been identified (median follow-up, 12 months). One interval ease of advanced lung adenocarcinoma occurred in a patient with negative initial screening results; one patient with multiple pulmonary nodules (biopsy findings positive for adenocarcinoma) proved to have primary renal cell carcinoma. Chest radiography and sputum cytology did not identify any cases that were not detected by LDSCT of the chest or AF. Three of eight intrathoracic cancers (38%) of the cases were identified by bronchoscopy alone.

AF has been used as an "up-front" method of screening high risk patients for central lung cancer in symptomatic smokers and patients with surgically cured aerodigestive tract cancers. (6) AF has also been used to screen for synchronous cancer in patients with known lung cancer, (7,8) and in patients with head and neck cancer. (9) In each of these studies, occult unsuspected intraepithelial brag cancers were identified. Our preliminary results add to this literature and suggest that an aggressive approach to proactive screening with AF is feasible in a defined high-risk population, and may offer improvement in case defection over spiral CT alone.

Table 1--Intratharacic Cancers Detected *

  Cell Type            Stage         LDSCT    AF

Small cell        Limited disease      +      +
Carcinoid                0             -      +
Squamous cell            0             -      +
Squamous cell            0             -      +
Adenocarcinoma          IA             +      -
Adenocarcinoma          IA             +      -
Adenocarcinoma         IIIB            -      -
Adenocarcinoma          IV             +      -

  Cell Type            Therapy                   Outcome Notes

Small cell        Chemoradiotherapy    Treatment ongoing
Carcinoid         PDT                  NED 1 yr
Squamous cell     Electrocautery       NED 1 yr
Squamous cell     Electrocautery       NED 3 mo
Adenocarcinoma    Lobectumy            NED 4 mo
Adenocarcinoma    Radiation            Brain metastasis at 2 mo, alive
                                         at 12 mo
Adenocarcinoma    Radiation            Died: interval case
Adenocarcinoma    Chemotherapy         Died: metastatic renal cancer

* + = cancer detected; - = no cancer detected; NED = no evidence of
disease; PDT = photodynamic therapy.

REFERENCES

(1) Petty TL, The early diagnosis of lung cancer. Dis Mon 2001; 47:204-264

(2) Diederich S, Wormanns D, Lenzen H, et al. Screening for asymptomatic early bronchogenic carcinoma with low dose CT of the chest. Cancer 2000 89(Suppl):2483-2484

(3) Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 1999; 354:99-105

(4) Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med 2002; 165:508-513

(5) Lam S, MacAulay C, leRiche JC, et al. Detection and localization of early lung cancer by fluorescence bronchoscopy. Cancer 2000; 89(Suppl):2468-2473

(6) Moro-Sibilot D, Jeanmart M, Lantuejoul S, et al. Cigarette smoking, preinvasive bronchial lesions, and autofluorescence bronchoscopy. Chest 2002; 122:1902-1908

(7) Paris C, Benichou J, Bota S, et al. Occupational and nonoccupational factors associated with high grade bronchial preinvasive lesions. Eur Respir J 2003; 21:332-344

(8) Weigel TL, Yousem S, Dacic S, et al. Fluorescence bronchoscopic surveillance after curative surgical resection for non-small-cell lung cancer. Ann Surg Oncol 2000; 7:176-180

(9) Venmans BJ, van Boxem TJ, Smit EF, et al. Bronchial intraepithelial neoplastic lesions in head and neck cancer patients: results of autofluorescence bronchoscopy. Ann Otol Rhinol Laryngol 2001; 110:635-638

* From the Department of Medicine (Dr. Loewen); Department of Cancer Prevention and Population Science (Drs. Reid and Mahoney, and Mr. Natarajan); Department of Pathology (Drs. Tan and Nava); Department of Diagnostic Radiology (Dr. Klippenstein); Roswell Park Cancer Institute, Buffalo, NY.

This research was supported in part by the Buffalo Oncologic Foundation, the Roswell Alliance, and the American Cancer Society.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Gregory M. Loewen, DO, FCCP, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton St, Buffalo, NY 14263: e-mail: gregory.loewen@roswellpark.org

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