Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy.

OBJECTIVES: Some patients and oncologists choose to treat localized esophageal cancer with definitive chemotherapy and radiation therapy rather than surgery. A subset of these patients have local relapse without distant metastases and therefore have no other curative intent treatment option but salvage esophagectomy. METHODS: We reviewed our experience with salvage esophagectomy from 1987 to 2000 at M.D. Anderson Cancer Center (n = 13, salvage after chemotherapy and radiotherapy group) and compared the data with those of patients receiving esophagectomy in a planned fashion 4 to 6 weeks after preoperative chemotherapy and radiation therapy (n = 99, preoperative chemotherapy and radiotherapy group). RESULTS: Increases in morbidity were seen after resection in the salvage after chemotherapy and radiotherapy group relative to the preoperative chemotherapy and radiotherapy group: mechanical ventilation (9.0 days vs 3.3 days, P =.08), intensive care unit stay (11.2 days vs 5.1 days, P =.07), hospital stay (29.4 days vs 18.4 days, P =.03), and anastomotic leak rates (5/13 [39%] vs 7/99 [7%], P =.005). Operative mortality (within 30 days) also tended to be increased statistically nonsignificantly (2/13 [15%] vs 6/99 [6%], P =.2). Salvage esophagectomy resulted in long-term survival (25% 5-year survival) in a subset of patients. Improved survival after salvage esophagectomy was associated with early pathologic stage (T1 N0, T2 N0), prolonged time to relapse, and R0 surgical resection. CONCLUSION: Patients who undergo salvage esophagectomy for relapse of tumor after definitive chemoradiation therapy have increased morbidity, mortality, and hospital use relative to patients undergoing planned esophagectomy after preoperative chemoradiation. Nevertheless, long-term survival can be achieved in this group, and such treatment should be considered for carefully selected patients at an experienced center.

Low intraindividual variability of cyclosporin A exposure reduces chronic rejection incidence and health care costs.

The present study applied a receiver operating characteristic (ROC) analysis to assess the role of intraindividual variability of cyclosporin A (CsA) drug exposure in predisposing renal transplant recipients to the occurrence of chronic rejection, as well as to increased health care costs using a resource-based economic analysis. Two hundred and four adult renal transplant recipients were treated with tapering doses of prednisone (Pred) and with a concentration-controlled strategy that selected doses of the olive oil-based formulations of CsA (Sandimmune(R)) that achieved target concentrations based on serial pharmacokinetic profiles. The ROC analysis revealed an inflection point of plots of the coefficient of variation (%CV) of CsA exposure versus the risk of chronic rejection at >/=28.4% for the average concentration (C(av)), i.e., the dosing interval-corrected area under the concentration-time curves, and >/=36% for the trough concentration (C(0)). The incidence of chronic rejection over a period of 5 yr was 24% among the less variable (LV) versus 40% among the variable (V) cohort. The economic analysis revealed that the total mean facility and physician costs per patient were $48,789 versus $60,998, respectively (P < 0.01). The degree of variability displayed by any individual could only be predicted by serial measurements of CsA concentrations, and not by demographic features, laboratory determinations, clinical characteristics, individual or mean values of any observed CsA concentration, or other pharmacokinetic parameters calculated following a single drug exposure. Thus, strategies that reduce intrapatient variability of CsA exposure over time may lead to reductions in chronic allograft loss and in treatment costs.