Circulating tumor cells in Hodgkin's lymphoma - a review of the spread of HL tumor cells or their putative precursors by lymphatic and hematogenous means, and their prognostic significance.
PURPOSE To examine the impact of extranodal chest wall and lung invasion on the prognosis of patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy. MATERIALS AND METHODS The outcome of 324 patients with clinical Stage I-II Hodgkin's lymphoma treated with combined modality therapy between 1981 and 1996 was analyzed. Twenty-two patients had chest wall invasion and 40 had invasion of lung parenchyma. The chemotherapy regimens used were ABVD in 182 patients (56%), MOPP/ABV(D) in 45 (14%), MOPP in 86 (27%), and other chemotherapy regimens in 11 patients (3%). This was followed by mantle/mediastinal radiotherapy (RT) in 163 patients (50%), extended-field RT in 135 patients (42%), and infradiaphragmatic RT in 26 patients (8%). The impact of chest wall and lung invasion on local relapse, disease-free survival, cause-specific survival, and overall survival was examined. RESULTS After a median follow-up of 8.3 years, the 5-year cause-specific and overall survival rate of the entire cohort was 93% and 90%, respectively. Compared with patients with no extranodal involvement, patients with chest wall invasion had significantly worse local control (89% vs. 68%, p = 0.005), disease-free survival (84% vs. 59%, p = 0.016), and cause-specific survival (94% vs. 86%, p = 0.009). Overall survival was also worse among patients with chest wall invasion, but not significantly so (90% vs. 82%, p = 0.10). Among the 16 patients with chest wall invasion but without lung invasion, 7 progressed during treatment or relapsed, 6 with local failure (crude relapse rate 44%, 95% confidence interval [CI] 19-68%), and 5 died (crude death rate 31%, 95% CI 9-54%). After adjusting for other significant prognostic factors, patients with chest wall invasion had significantly worse local control (hazard ratio 2.8, 95% CI 1.2-6.3), disease-free survival (hazard ratio 2.3, 95% CI 1.1-4.8), and cause-specific survival (hazard ratio 2.8, 95% CI 1.1-6.8). Lung invasion was not significantly associated with any of the outcomes assessed. CONCLUSIONS Chest wall invasion is an adverse prognostic factor among clinical Stage I-II Hodgkin's lymphoma patients treated with combined modality therapy, although we did not find a worse outcome for patients with lung invasion. Efforts to reduce treatment intensity in these patients should be undertaken with caution, recognizing their increased risk of local relapse.