Serum copper concentration as an index of clinical lung injury

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.