Mariela A. Blum Murphy

Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival—The University of Texas MD Anderson Cancer Center experience

Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence‐free survival (RFS), and patterns of recurrence in a large cohort from a single institution.

The impact of histology on recurrence patterns in esophageal cancer treated with definitive chemoradiotherapy

BACKGROUND To assess the impact of histology on recurrence patterns and survival outcomes in patients with esophageal cancer (EC) treated with definitive chemoradiotherapy (CRT). METHODS We analyzed 590 consecutive EC patients who received definitive CRT from 1998 to 2014, including 182 patients (30.8%) with squamous cell carcinoma (SCC) and 408 (69.2%) with adenocarcinoma. Recurrence pattern and timing, survival, and potential prognostic factors were compared. RESULTS After a median follow-up time of 58.0months, the SCC group demonstrated a comparable locoregional recurrence rate (42.9% vs. 38.0%, P=0.264) but a significantly lower distant failure rate (27.5% vs. 48.0%, P<0.001) than adenocarcinoma group. No significant difference was found in overall survival or locoregional failure-free survival between groups, whereas the SCC group was associated with significantly more favorable recurrence-free survival (P=0.009) and distant metastasis-free survival (P<0.001). The adenocarcinoma group had higher hematogenous metastasis rates of bone, brain, and liver, whereas the SCC group had a marginally higher regional recurrence rate. Among patients who received salvage surgery after locoregional recurrence, no significant difference in survival was found between groups (P=0.12). CONCLUSIONS The patterns and sites of recurrence, survival outcomes, and prognostic factors were significantly different between esophageal SCC and adenocarcinoma.

101 Long-Term Survivors Who Had Metastatic Gastroesophageal Cancer and Received Local Consolidative Therapy

Background: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation with/without surgery) in selected patients with metastatic gastroesophageal carcinoma (mGEAC). Only after a consensus during multidisciplinary discussions, local therapy was initiated. Methods: We identified 101 patients with mGEAC who had local consolidation. We evaluated the association between various clinical variables (location of the primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose) and overall survival (OS). Results: Of 101 patients, 71 had a proximal primary (esophageal, Siewert type I or II), and 30 patients had a distal primary (Siewert type III or distal). The median OS was 25.7 months (95% confidence interval [CI] 22.3-32.8). The OS rates at 2 and 5 years were 53.8% (95% CI 44.7-64.8) and 20.7% (95% CI 13.4-31.9), respectively. OS was highly associated with the location of the primary (median of 22.8 months for Siewert I/II vs. 41.5 months for Siewert III or distal, p = 0.03). The duration of initial chemotherapy was highly associated with OS (median of 21.8 months for <3 months vs. 32.5 months for ≥3 months, p = 0.004). Conclusion: Some mGEAC patients with a favorable clinical course can achieve a ∼20% 5-year survival rate with an approach that uses initial chemotherapy followed by multidisciplinary discussion to proceed with consolidation with local therapy. Patients with distal GEAC and those who receive initial chemotherapy for ≥3 months are the maximum beneficiaries.

Patterns of relapse in patients with localized gastric adenocarcinoma who had surgery with or without adjunctive therapy: Costs and effectiveness of surveillance

Purpose After therapy of localized gastric adenocarcinoma (GAC) patients, the costs of surveillance, relapse patterns, and possibility of salvage are unknown. Materials and Methods We identified 246 patients, who after having a negative peritoneal staging, received therapy (any therapy which included surgery) and were surveyed (every 3–6 months in the first 3 years, then yearly; ∼10 CTs and ∼7 endoscopies per patient). We used the 2016 Medicare dollars reimbursed as the “costs” for surveillance. Results Common features were: Caucasians (57%), men (60%), poorly differentiated histology (76%), preoperative chemotherapy (74%), preoperative chemoradiation (59%), and had surgery (100%). At a median follow-up of 3.7 years (range, 0.1 to 18.3), the median overall survival (OS) was 9.2 years (95% CI, 6.0 to 11.2). Tumor grade (p = 0.02), p/yp stage (p < 0.001), % residual GAC (p = 0.05), the R status (p = 0.01), total gastrectomy (p = 0.001), and relapse type (p = 0.02) were associated with OS. Relapse occurred in 79 (32%) patients (only 8% were local-regional) and 90% occurred within 36 months of surgery. P/yp stage (p < 0.001) and total gastrectomy (p = 0.01) were independent prognosticators for OS in the multivariate analysis. Only 1 relapsed patient had successful salvage therapy. The estimated reimbursement for imaging studies and endoscopies was

Recurrence Risk Stratification After Preoperative Chemoradiation of Esophageal Adenocarcinoma

1,761,221.91 (marked underestimation of actual costs). Conclusions The median OS of localized GAC patients was excellent with infrequent local-regional relapses. Rigorous surveillance had a low yield and high “costs”. Our data suggest that less frequent surveillance intervals and limiting expensive investigations to symptomatic patients may be warranted.

Barrett’s Esophagus after Bimodality Therapy in Patients with Esophageal Adenocarcinoma

Objective: To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT). Background: Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce. Methods: Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients. Results: A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort. Conclusions: We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

Gastroesophageal Cancer During Pregnancy: a Case Report and Review of the Literature

Introduction: Barrett’s esophagus (BE) may be present in patients with esophageal adenocarcinoma (EAC) after bimodality therapy (BMT). There is no specific guidance for follow-up of these patients with regard to the presence of BE or dysplasia. In this study, we assessed the outcomes of patients who, after BMT, had BE and those who did not. Method: Patients with EAC who had BMT were identified and analyzed retrospectively in two groups, with and without BE. We compared patient characteristics and outcome variables (local, distant, and no recurrence). Results: Of 228 patients with EAC, 68 (29.8%) had BE before BMT. Ninety-eight (42.9%) had BE after BMT, and endoscopic intervention was done in 11 (11.2%). With a median follow-up of 37 months, the presence of post-BMT BE was not significantly associated with overall survival (OS) and local recurrence-free survival (LRFS). Similarly, endoscopic intervention was not significantly associated with OS and LRFS. Fifty (73.5%) patients with BE before BMT had BE after BMT (p < 0.0001). Conclusion: The presence of BE after BMT was not associated with increased risk of local recurrence. The local recurrence rate was not influenced by endoscopic intervention. Prospective studies are warranted to generate guidance for intervention, if necessary, for this group of EAC patients.

The role of chemotherapy in unresectable or metastatic adenocarcinoma of the stomach and gastroesophageal junction

Incidence of cancer during pregnancy is likely increased nowadays in developed societies and clinical practice due to women’s increasing trend toward late childbirth [1]. While cancer develops in approximately 1 to 2 per 1000 pregnant women, the diagnosis of esophageal or gastric cancer during pregnancy or the lactation period is very rare, accounting for only 0.026 to 0.1% of all pregnancies [2]. Gastroesophageal junction (GEJ) cancer diagnosis during pregnancy is usually delayed due to low index of suspicion for having a malignant disease at a young age. Symptoms such as abdominal pain, nausea, vomiting, and fatigue can be mistaken as part of physiologic gestational symptoms and anemia as a laboratory finding. Additionally, this group of patients has some distinct features that may affect disease course such as being of young age, female gender, mostly being diagnosed at advanced stage, having a passive attitude toward treatment due to concerns about fetal health, and increased treatment challenges during pregnancy [3]. Early diagnosis allows appropriate management with a multidisciplinary approach. Contemporary evidence suggest that chemotherapy can safely be given starting at 12 to 14 weeks of gestational age and radiotherapy of upper body parts, with adequate shielding, is expected to be safe during the first and second trimesters of pregnancy if the tumor is located sufficiently far from the fetus [4]. Low-risk surgery during pregnancy is feasible in all trimesters of pregnancy [5, 6]. Here, we report a case of gastroesophageal cancer diagnosed during pregnancy, the multidisciplinary management, and update of the literature. We also conducted a search on PubMed using Bgastric cancer^ AND Bpregnancy,^ and Bgastroesophageal cancer^ AND Bpregnancy^ as keywords beginning 1998 to 2017. Hits were carefully examined and two publications excluded as duplicate.

Long-term survival and toxicity outcomes of intensity modulated radiation therapy for the treatment of esophageal cancer: A large single-institutional cohort study

Gastric cancer including gastroesophageal junction adenocarcinomas are most challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly diagnosed patients will have disseminated disease and in need of systemic therapy. Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with differences in geographical distribution, histopathology, and molecular subtypes. Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory irinotecan are active drugs against AGC. The combination of fluoropyrimidines with a platinum compound is the optimal first-line treatment. Trastuzumab (given in combination with chemotherapy for HER2 positive tumors) and ramucirumab are the only targeted agents approved by the food and drug administration for the treatment in AGC for first and second line respectively. Efforts are being directed to harness the immune system with checkpoint inhibitors and to combining these drugs with chemotherapy in clinical trials. Genomic technology advancements might provide us with the tools to create personalized treatment for AGC in the near future with the goal to improve outcomes. In this article we aimed to review current therapeutic regimens for AGC with an update of ongoing clinical trials.

A Phase I/II Study of Docetaxel, Oxaliplatin, and Fluorouracil (D-FOX) Chemotherapy in Patients With Untreated Locally Unresectable or Metastatic Adenocarcinoma of the Stomach and Gastroesophageal Junction.

Purpose In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC. Methods and materials This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications. Results The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%). Conclusions This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.