Recurrence of Bronchioloalveolar Carcinoma in Transplanted Lungs

Reviewers: Kenneth Blank, MD
Source: The New England Journal of Medicine Volume 340, Number 14: April 8, 1999

Background

Bronchioloalveolar lung cancer is characterized pathologically by cancer cells lining the lung alveoli while preservinginterstitial lung tissue. Bronchioloalveolar lung cancer is widely believed to be a variant of adenocarcinoma of the lungbut recent data indicate it has a natural history and prognosis distinct from adenocarcinoma. The five-year survival forbronchioloalveolar is higher than for adenocarcinoma and metastases within the lung- to ipsilateral lobes or thecontralateral lung- is more frequent in bronchioloalveolar lung cancer. Because conventional therapy rarely curesbronchioloalveolar lung cancer and because of the likelihood of spread within the lung tissue, physicians at Universityof Alabama Birmingham performed lung transplantation in the treatment of patients with bronchioloalveolar lungcancer. Their findings are reported in the April 8, 1999 issue of The New England Journal of Medicine.

Materials and Methods

Eligible patients had to have biopsy proven bronchioloalveolar lung cancer and no evidence of extrapulmonaryspread. All patients underwent removal of one or both lungs and transplantation with one or two lungs from acadaver. Post-operative care was similar to other lung transplant patients. Three patients underwent genetic analysisof their tumors with polymerase chain reaction amplification of microsatellite regions and southern blot analysis.

Results

Three of the seven patients had previously been treated by conventional resection only to have their tumor recur 4 to17 months later. Four patients had tumor spread to another lung lobe and were therefore not candidates forconventional surgery.

Of the seven patients, four had tumor recurrences at 10, 10, 39 and 48 months after transplant surgery. Of these fourpatients, all recurred in the transplanted lung. Three have been subsequently treated with surgical resection and tworemain alive at 4 and 18 months after the salvage surgery. One patient who relapsed underwent a second lungtransplant but died of pulmonary complications and recurrent tumor nine months after the second transplant. Of thethree patients without evidence of tumor relapse, two are alive at 50 and 62 months after lung transplant surgery.

Genetic studies on the original tumor and recurrences in three patients were undertaken to determine if the recurrencewas a new primary or a true recurrence. In two patients amplified fragments of DNA were nearly identical to theoriginal lung tumor and clearly distinct from the transplanted tissue. In the third patient the DNA more closelyresembled the original tissue but some differences were noted.

Conclusion

Four of the seven patients were free of disease for at least three years following lung transplantation, and two patientswere alive and free of disease greater than 50 months. Genetic analysis performed in three of the four patients whorecurred strongly suggested that the recurrence originated from the original bronchioloalveolar lung cancer and notfrom the donor lung. These results compare favorably to retrospective reviews using conventional surgery plus orminus chemotherapy. However, any group of patients with lung cancer that can tolerate the rigors of transplantsurgery is certainly a select bunch.