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Background: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/ unpredictable outcomes. Predictive clinical variables/ biomarkers are not established. Methods: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or

Background: In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS). Methods: We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis. Results: The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (≤6; p = 0.0017). Patients with a high iSUV (>6) had a longer OS compared to those with a low iSUV (≤6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV >6 (hazard ratio = 0.26). Conclusion: Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. Methods: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. Results: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (≥4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). Conclusion: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We have limited knowledge of the geographic distribution of resistant esophageal adenocarcinoma (EAC) in resected specimens, but its clinical importance can be enormous. Method: We selected patients with baseline stage III EAC who had had chemoradiation followed by surgery and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (percentage of resistant EAC and anatomic distribution). Results: A total of 100 clinical stage III patients were studied; 90% had an R0 resection, and 99% had either moderate or poorly differentiated EAC. Twelve percent had >50% residual cancer, 31% had 11-50% residual cancer, 53% had 1-10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa (66%), muscularis propria (76%), and serosa (62%); all compartments were involved in 35% of the cases. Lack of EAC (meaning response) was observed in the mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery showed no EAC in 79% of the patients, in the surgical specimens, resistant EAC was frequently occurring in the mucosa/submucosa (66%). Conclusion: Contrary to our hypothesis that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the postchemoradiation biopsies are misleading, and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim: Malignant nodes in patients with localized esophageal adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the correlation of the distribution of nodes with the outcome of patients undergoing chemoradiation/surgery (trimodality therapy). Methods: We studied 209 L-EAC patients who had confirmed or suspicious nodes at baseline staging. All patients received trimodality therapy and were grouped according to the nodal geography: above the diaphragm (AD), below the diaphragm (BD), or above and below the diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier method, and the outcomes of the groups were assessed by the log-rank test. Results: Patients were primarily Caucasian (91%) and male (93%), with a baseline stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4-11.7). Of the 209 patients, 35% (n = 73) had AD nodes, 20% (n = 41) had BD nodes, and 45% (n = 95) had ABD nodes. ABD patients had a 5-year overall survival rate of 33%, whereas this rate was 55% in AD patients and 60% in BD patients (p = 0.02). Patients with a higher histology grade were also at a higher risk of relapse and had a poor survival (p < 0.01 for both). Conclusions: L-EAC patients in the ABD group had the worst outcome after trimodality treatment compared to those in the AD or BD group. Novel strategies are needed for ABD patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common but the details of their distribution and timing in a large cohort have not been described. Methods: 629 patients with localized EAC who had TMT or BMT were analyzed. Standard statistical methods were used to define the end points. Results: The median follow-up time was 37.2 months (interquartile range 17.8-65.0). Of 356 TMT patients, 33% (119) developed DM as their first relapse and of 273 BMT patients, 40% (109) developed DM; 91% (TMT) and 96% (BMT) of the DMs were diagnosed within 2 years of local therapy. The most common sites of DM were: lung, distant nodes, liver, peritoneal cavity, bone, brain and pleura in order of frequency. The median overall survival of TMT patients with DM was 10.2 months (95% CI 7.8-12.7) and that for BMT patients with DM was 7.8 months (95% CI 5.7-9.9). Conclusions: Following TMT or BMT, ≥33% of patients developed DMs and most of these occurred within 2 years (>90%) of local therapy. A clinical model is desirable that associates clinical parameters with a high risk for DM in TMT-eligible patients prior to surgery. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: It is unclear whether patients undergoing trimodality therapy (TMT) should be screened or surveyed for brain metastases. Methods: We retrospectively analyzed esophageal cancer (EC) patients who underwent TMT between the years 2000 and 2010. All were systematically staged and surveyed but none had screening or surveillance brain imaging. Results: The median follow-up time for 518 patients was 29.3 months (range 1-149.2); all patients had adenocarcinoma of the esophagus. Of 188 (36.3%) patients who developed distant metastases, 20 (10.6% of 188 patients or 3.9% of 518 patients) had brain metastases. A higher baseline clinical stage (stage III or IVa) was associated with brain metastases. Most (90%) patients with brain metastases were diagnosed within 24 months of surgery. Sixteen patients had central nervous system symptoms at diagnosis. Twelve (60%) patients had solitary metastasis and 8 (40%) patients had multiple metastases. Although 17 patients received therapy for brain metastases, the median overall survival time of 20 patients was only 10.5 months (95% CI 6.6-14.0). Conclusion: After TMT, 3.9% of EC patients developed brain metastases and their prognosis was poor. Our data suggest that screening and/or surveillance for brain metastases in the EC population undergoing TMT is not warranted. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Trimodality therapy (TMT; chemoradiation plus surgery) has level-1 evidence for survival advantage for TMT-eligible esophagogastric cancer patients. Some patients, however, decline surgery after preoperative chemoradiation. The question of which patient should have esophagectomy and which one should not is unlikely to be answered by a prospective comparison; therefore, we matched the clinical covariates of several patients who had surgery with those who declined surgery (DS). Methods: Between 2002 and 2011, we identified 623 patients in our databases. Of 623 patients, 244 patients had TMT and 61 TMT-eligible patients were in the DS group. Using the propensity-score method, we matched 16 covariates between 36 DS patients and 36 TMT patients. Results: Baseline characteristics between the two groups were balanced (p = NS). The median overall survival times were: 57.9 months (95% CI: 27.7 to not applicable, NA) for the DS group and 50.8 months (95% CI: 30.7 to NA) for the TMT group (p = 0.28). The median relapse-free survival times were: 18.5 (95% CI: 11.5-30.4) for the DS group and 26.5 months (95% CI: 15.5-NA) for the TMT group (p = 0.45). Eleven (31%) of 36 patients in the DS group had salvage surgery. Conclusions: Our results are intriguing but skewed by the patients who had salvage surgery in the DS group. Until highly reliable predictive models are developed for esophageal preservation, TMT must be encouraged for all TMT-eligible gastroesophageal cancer patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS). Materials and methods Thirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS. Results Among the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9–NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR ( p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG ( p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS ( p = 0.01 and 0.03, respectively). Conclusion None of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS. [ABSTRACT FROM AUTHOR]

Abstract: Background: The presence of malignant lymph nodes (+ypNodes) in the surgical specimen after preoperative chemoradiation (trimodality) in patients with oesophageal cancer (EC) portends a poor prognosis for overall survival (OS) and disease-free survival (DFS). Currently, none of the clinical variables highly correlates with +ypNodes. We hypothesised that a combination of clinical variables could generate a model that associates with high likelihood of +ypNodes after trimodality in EC patients. Methods: We report on 293 consecutive EC patients who received trimodality therapy. A multivariate logistic regression analysis that included pretreatment and post-chemoradiation variables identified independent variables that were used to construct a nomogram for +ypNodes after trimodality in EC patients. Results: Of 293 patients, 91 (31.1%) had +ypNodes. OS (p =0.0002) and DFS (p <0.0001) were shorter in patients with +ypNodes compared to those with –ypNodes. In multivariable analysis, the significant variables for +ypNodes were: baseline T-stage (odds ratio [OR], 7.145; 95% confidence interval [CI], 1.381–36.969; p =0.019), baseline N-stage (OR, 2.246; 95% CI, 1.024–4.926; p =0.044), tumour length (OR, 1.178; 95% CI, 1.024–1.357; p =0.022), induction chemotherapy (OR, 0.471; 95% CI, 0.242–0.915; p =0.026), nodal uptake on post-chemoradiation positron emission tomography (OR, 2.923; 95% CI, 1.007–8.485; p =0.049) and enlarged node(s) on post-chemoradiation computerised tomography (OR, 3.465; 95% CI, 1.549–7.753; p =0.002). The nomogram after internal validation using the bootstrap method (200 runs) yielded a high concordance index of 0.756. Conclusion: Our nomogram highly correlates with the presence of +ypNodes after chemoradiation, however, considerably more refinement is needed before it can be implemented in the clinic. [Copyright &y& Elsevier]