Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.
Elena Elimova, Roopma Wadhwa, Hironori Shiozaki, Kazuki Sudo, Jeannelyn S. Estrella, Brian D. Badgwell, Prajnan Das, Aurelio Matamoros Jr, Shumei Song and Jaffer A. Ajani
Takashi Taketa, Kazuki Sudo, Arlene M. Correa, Roopma Wadhwa, Hironori Shiozaki, Elena Elimova, Maria-Claudia Campagna, Mariela A. Blum, Heath D. Skinner, Ritsuko U. Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian R. Weston, David C. Rice, Stephen G. Swisher, Dipen M. Maru, Wayne L. Hofstetter and Jaffer A. Ajani
Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemoradiation and surgery (trimodality therapy [TMT]) remain empiric. The authors hypothesized that the frequency, type, and timing of relapses after TMT would be highly associated with surgical pathology stage (SPS), and therefore SPS could be used to individualize the surveillance strategy. Between 2000 and 2010, 518 patients with EAC were identified who underwent TMT at The University of Texas MD Anderson Cancer Center and were frequently surveyed. Frequency, type, and timing of the first relapse (locoregional and/or distant) were tabulated according to SPS. Standard statistical approaches were used. The median follow-up time after esophageal surgery was 55.4 months (range, 1.0-149.2 months). Disease relapse occurred in 215 patients (41.5%). Higher SPS was associated with a higher rate of relapse (0/I vs II/III, P≤.001; 0/I vs II, P=.002; SPS 0/I vs III, P≤.001; and SPS II vs III, P=.005) and with shorter time to relapse (P<.001). Irrespective of the SPS, approximately 95% of all relapses occurred within 36 months of surgery. The 3- and 5-year overall survival rates were shorter for patients with a higher SPS than those with a lower SPS (0/I vs II/III, P≤.001; 0/I vs II, P≤.001; 0/I vs III, P≤.001; and II vs III, P=.014). The compelling data show an excellent association between SPS and frequency/type/timing of relapses after TMT in patients with EAC. Thus, the surveillance strategy can potentially be customized based on SPS. These data can inform a future evidence-based surveillance strategy that can be efficient and cost-effective.
Kazuki Sudo, Xuemei Wang, Lianchun Xiao, Roopma Wadhwa, Hironori Shiozaki, Elena Elimova, David C. Rice, Jeffrey H. Lee, Brian Weston, Manoop S. Bhutani, Adarsh Hiremath, Nikolaos Charalampakis, Ritsuko Komaki, Mariela A. Blum, Stephen G. Swisher, Dipen M. Maru, Heath D. Skinner, Jeana L. Garris, Jane E. Rogers, Wayne L. Hofstetter and Jaffer A. Ajani
Background: Among patients with localized esophageal cancer (LEC), 35% or more develop distant metastases (DM) as first relapse, most in the first 24 months after local therapy. Implementation of novel strategies may be possible if DM can be predicted reliably. We hypothesized that clinical variables could help generate a DM nomogram. Patients and Methods: Patients with LEC who completed multimodality therapy were analyzed. Various statistical methods were used, including multivariate analysis to generate a nomogram. A concordance index (c-index) was established and validated using the bootstrap method. Results: Among 629 patients analyzed (356 trimodality/273 bimodality), 36% patients developed DM as first relapse. The median overall survival from DM was only 8.6 months (95% CI, 7.0–10.2). In a multivariate analysis, the variables associated with a higher risk for developing DM were poorly differentiated histology (hazard ratio [HR], 1.76; P<.0001), baseline T3/T4 primary (HR, 3.07; P=.0006), and baseline N+ LEC (HR, 2.01; P<.0001). Although variables associated with a lower risk for DM were age of 60 years or older (HR, 0.75; P=.04), squamous cell carcinoma (HR, 0.54; P=.013), and trimodality therapy (HR, 0.58; P=.0001), the bias-corrected c-index was 0.67 after 250 bootstrap resamples. Conclusions: Our nomogram identified patients with LEC who developed DM with a high probability. The model needs to be refined (tumor and blood biomarkers) and validated. This type of model will allow implementation of novel strategies in patients with LEC.