J.P. Williams

Circulating IL-6 as a predictor of radiation pneumonitis.

PURPOSE We report results from a clinical research protocol investigating circulating pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFalpha]) in relation to radiation pulmonary injury. METHODS AND MATERIALS In a protocol for cytokine measurement, 25 patients had clinical follow-up longer than 12 months, and 24 had serial cytokine data. Serial plasma specimens before, during, and after thoracic radiotherapy were analyzed for IL-6 and TNFalpha using enzyme-linked immunosorbent assay (ELISA). Radiation pulmonary injury was defined using National Cancer Institute Common Toxicity Criteria. RESULTS Of the 24 patients, 6 had Grade 1 pneumonitis, and 13 had Grade 2 pneumonitis. There was no Grade 3/4 pneumonitis. Median time of radiation pneumonitis was between 8 and 12 weeks post-therapy. IL-6 levels before, during, and after thoracic radiation therapy were significantly higher in those who developed pneumonitis. In contrast, we did not detect a significant correlation between plasma TNFalpha and radiation pneumonitis. CONCLUSIONS High pretreatment plasma levels of IL-6 predisposed patients to the risk of radiation pneumonitis. Pretreatment IL-6 level may serve as a predictor for radiation pneumonitis. Serial plasma IL-6 was consistently higher for the pneumonitis group. The role of IL-6 in the cytokine cascades that promote radiation pulmonary injury deserves further investigation.

Risk of second aerodigestive cancers increases in patients who survive free of small-cell lung cancer for more than 2 years.

PURPOSE Patients who survived small-cell lung cancer (SCLC) for more than 2 years were evaluated to determine the frequency and anatomic pattern of redevelopment of small-cell cancer and development of non-small-cell lung cancer (NSCLC) and aerodigestive cancers with the passage of time. PATIENTS AND METHODS From April 1973 through December 1991, 578 patients with previously untreated SCLC were entered onto prospective therapeutic trials at the National Cancer Institute (NCI), Bethesda, MD. Sixty-two (11%) were cancer-free 2 years after initiation of therapy and were assessable for redevelopment of SCLC and development of NSCLC, and aerodigestive cancers. RESULTS Twenty patients redeveloped SCLC 2.0 to 12.2 years after initiation of chemotherapy, of whom two patients were deemed to have a second primary small-cell cancer that involved the aerodigestive tract. Fifteen patients developed 16 cancers in the lung other than SCLC 3.4 to 14.9 years after initiation of therapy. Two developed other aerodigestive cancers that involved the larynx and lip. The risk of a NSCLC and aerodigestive cancer in these patients increased more than sixfold from 2% per patient per year during years 2 to 4 to 12.6% and 14.4%, respectively, after more than 10 years. The cumulative actuarial risk of a second primary NSCLC or aerodigestive cancer at 16 years is 69% and 72%, respectively. CONCLUSION The increasing risk of second aerodigestive cancers with the passage of time is a mounting problem for patients cured of SCLC. Chemoprevention trials for these patients should be considered.