Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It?

OBJECTIVE: We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy. BACKGROUND: Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown. METHODS: From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. RESULTS: Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival. CONCLUSIONS: Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.

Value of Lymphadenectomy in Patients Receiving Neoadjuvant Therapy for Esophageal Adenocarcinoma.

OBJECTIVE: The aim of this study was to assess the effect on survival of extent of lymphadenectomy during esophagectomy for patients undergoing multimodality (neoadjuvant) therapy for adenocarcinoma of the esophagus and esophagogastric junction using Worldwide Esophageal Cancer Collaboration data. SUMMARY BACKGROUND DATA: Previous worldwide data demonstrated that optimum lymphadenectomy during esophagectomy alone for esophageal cancer provides accurate staging and maximum survival. However, for patients undergoing neoadjuvant therapy for locally advanced adenocarcinoma, its value is unclear, leading to wide practice variability. METHODS: A total of 3859 patients with adenocarcinoma of the esophagus or esophagogastric junction received neoadjuvant therapy. The endpoint was all-cause mortality, reported as gain or loss of lifetime within 10 years. Lifetime predicted for each regional lymph node resected used quantile survival random forest methodology. RESULTS: Across all post-neoadjuvant ypTNM cancer categories, some degree of lymphadenectomy was associated with longer lifetime, but in a nonlinear fashion. For patients with ypN0 cancers, there was a modest gain in lifetime up to 25 lymph nodes resected and an incremental loss in lifetime as >25 were resected. For patients with ypN+ cancers, there was a robust gain in lifetime up to 30 lymph nodes resected and then an incremental loss in lifetime. CONCLUSIONS: Worldwide data for adenocarcinoma of the esophagus and esophagogastric junction demonstrate that lymphadenectomy during esophagectomy is a valuable component of neoadjuvant therapy. Survival is maximized when an optimum range of nodes is resected.

Durability and Performance of 2298 Trifecta Aortic Valve Prostheses: A Propensity-Matched Analysis.

BACKGROUND: Reports of early failure of the Trifecta externally wrapped, bovine pericardial aortic valve prosthesis (Abbott Laboratories, Abbott Park, IL) raise concerns about its durability. This study evaluated the hemodynamic performance and explant of Trifecta valves compared with the PERIMOUNT bovine pericardial prosthesis (Edwards Lifesciences, Irvine, CA). METHODS: From October 2007 to July 2017, 2305 patients received a Trifecta bioprosthesis during aortic valve replacement at Cleveland Clinic. Trends in postoperative valve hemodynamics were assessed from 4971 transthoracic echocardiograms and valve explants by systemic follow-up. To compare outcomes, 2298 patients receiving a Trifecta valve were 1:1 propensity matched from 17,281 patients receiving a PERIMOUNT bioprosthesis. RESULTS: Mean age at implant was 69 years in both matched groups. Compared with PERIMOUNT valves, early transvalvular mean gradient of Trifecta valves was lower (11 vs 15 mm Hg at 1 year, P < .001); however, its longitudinal rate of rise was greater (P < .001), resulting in 5-year mean gradients of 17 vs 16 mm Hg, and more patients experienced severe aortic regurgitation (2.4% vs 0.81%; P < .001). At 5 years, 35 Trifecta valves had been explanted vs 14 PERIMOUNT valves; freedom from explant at 1, 3, and 5 years was 98.9%, 98.0%, and 95.9%, respectively, for the Trifecta group vs 99.3%, 99.0%, and 98.7% for the PERIMOUNT group (P < .001). CONCLUSIONS: Compared with an older-generation internally mounted bovine pericardial valve, the Trifecta externally wrapped bioprosthesis exhibits superior early hemodynamic performance, but has a rapid increase in transvalvular gradient and more aortic regurgitation, with lower freedom from explant at 5 years. These findings raise concern regarding long-term Trifecta durability despite favorable early hemodynamics.