Outcome Of Esophageal Cancer Patients Research Articles

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

Concomitant preoperative airflow obstruction confers worse prognosis after trans-thoracic surgery for esophageal cancer.

Airflow obstruction is a critical element of chronic airway diseases. This study aimed to evaluate the impact of preoperative airflow obstruction on the prognosis of patients following surgery for esophageal carcinoma. A total of 821 esophageal cancer patients were included and classified into two groups based on whether or not they had preoperative airflow obstruction. Airflow obstruction was defined as a forced expiration volume in the first second (FEV1)/forced vital capacity (FVC) ratio below the lower limit of normal (LLN). A retrospective analysis of the impact of airflow obstruction on the survival of patients with esophageal carcinoma undergoing esophagectomy was performed. Patients with airflow obstruction (102/821, 12.4%) had lower three-year overall (42/102, 58.8%) and progression-free survival rate (47/102, 53.9%) than those without airflow obstruction (P < 0.001). Multivariate analyses showed that airflow obstruction was an independent risk factor for overall survival (Hazard Ratio = 1.66; 95% CI: 1.17-2.35, P = 0.004) and disease progression (Hazard Ratio = 1.51; 95% CI: 1.1-2.08; P = 0.01). A subgroup analysis revealed that the above results were more significant in male patients, BMI < 23 kg/m2 patients or late-stage cancer (stage III-IVA) (P = 0.001) patients and those undergoing open esophagectomy (P < 0.001). Preoperative airflow obstruction defined by FEV1/FVC ratio below LLN was an independent risk factor for mortality in esophageal cancer patients after trans-thoracic esophagectomy. Comprehensive management of airflow obstruction and more personalized surgical decision-making are necessary to improve survival outcomes in esophageal cancer patients.

Galectins in Esophageal Cancer: Current Knowledge and Future Perspectives.

Esophageal cancer is a disease with poor overall survival. Despite advancements in therapeutic options, the treatment outcome of esophageal cancer patients remains dismal with an overall 5-year survival rate of approximately 20 percent. To improve treatment efficacy and patient survival, efforts are being made to identify the factors that underlie disease progression and that contribute to poor therapeutic responses. It has become clear that some of these factors reside in the tumor micro-environment. In particular, the tumor vasculature and the tumor immune micro-environment have been implicated in esophageal cancer progression and treatment response. Interestingly, galectins represent a family of glycan-binding proteins that has been linked to both tumor angiogenesis and tumor immunosuppression. Indeed, in several cancer types, galectins have been identified as diagnostic and/or prognostic markers. However, the role of galectins in esophageal cancer is still poorly understood. Here, we summarize the current literature with regard to the expression and potential functions of galectins in esophageal cancer. In addition, we highlight the gaps in the current knowledge and we propose directions for future research in order to reveal whether galectins contribute to esophageal cancer progression and provide opportunities to improve the treatment and survival of esophageal cancer patients.

Impact of oral nutrition supplementation on outcomes of esophageal cancer patients treated with chemotherapy: A retrospective cohort study with propensity score matching.

There is a lack of evidence regarding the outcomes of oral nutrition supplementation (ONS) in patients with esophageal cancer (EC) who received chemotherapy treatment. The aim of this study was to perform a retrospective cohort study by comparing an adequate ONS group with a control group. The study was performed in the Oncology Department of West China Hospital of Sichuan University. Patients at nutritional risk were identified from March 2016 to June 2019, and divided into an ONS group and a control group. To control for potential confounding variables, the propensity score method with matching was carried out. The main outcomes were length of stay (LOS) and hospitalization cost. Secondary outcomes included the incidence of pulmonary infection and myelosuppression. Out of 5,316 hospitalizations, a one-to-one matched sample was created (N = 229). The pathological tumor, node, metastasis (pTNM) stage of patients ranged from II to IV. A total of 69 patients received ONS, and 160 patients did not receive ONS. The incidence of myelosuppression in the ONS group and the control group was 4.3 vs. 17.4% (P = 0.014), respectively. However, ONS was associated with a 2 days increase in LOS, from 7 to 9 days (P < 0.000) and a hospitalization cost increase of $731, from $1134 to $1865 (P = 0.005). No statistical differences were observed in the incidence of pulmonary infection between the two groups. Further subgroup analysis based on body mass index (BMI) showed that at BMI ≤ 18.5 kg/m2, the incidence of myelosuppression in the ONS group was lower than that in the control group (3.0 vs. 20.8%, P = 0.022). At BMI > 18.5 kg/m2, no statistical differences were observed in the incidence of myelosuppression between the two groups. Although ONS increases hospitalization cost and LOS, it may be associated with reduced myelosuppression incidence, especially for patients with a BMI ≤ 18.5 kg/m2.

441. ESOPHAGEAL CANCER MANAGEMENT IN A SWISS REFERRAL CENTER; A 20-YEAR EXPERIENCE

Abstract In the past decades, management of esophageal cancer (EC) has significantly changed with the widespread use of oncological treatments, as well as minimally invasive surgery and enhanced recovery protocols. Concurrently, the histological type, comorbidity status and life expectency of the ‘typical’ EC patient have also evolved. The aim of this study was to assess the evolution in epidemiology, management and outcomes of EC patients treated in a Swiss tertiary referral center the last 20 years. Baseline demographics, clinico-pathological data, treatment details and postoperative outcomes were retrieved from our institutional prospective database for all consecutive patients operated for esophageal cancer with curative intent. Emergency surgery and endoscopic treatment of early EC were excluded, hence 332 patients (265 male, 67 female) were included in the final analysis. Patients were divided in 3 groups: ‘historical group’: 2000–2007, n = 73; ‘transition group’: 2008–2014, n = 108; ‘modern group’: 2015–2020, n = 151. Comparison was performed with the x2 test for discrete and the ANOVA tests for continuous variables, with the Bonferroni method to determine significance in pairwise comparisons (p &amp;lt; 0.05). The annual caseload doubled (10 to 25 cases/y). Alcohol consumption (57.5% to 28.5%, p &amp;lt; 0.001), active smoking (64.4% to 38.4%, p = 0.001) and COPD (41.1% to 35.1%, p = 0.05) decreased. Squamous cell carcinoma (58.9% historic, 34.4% modern group) was replaced by adenocarcinoma as the most prevalent type (35.6% vs 64.2%, p = 0.001). Detection of locally advanced disease increased from 58.8% to 75.8% (p = 0.022), along with the use of neoadjuvant treatment (34.2% historic, 83.4% modern group, p &amp;lt; 0.001). Major postoperative morbidity was documented in 34.2% of patients (historic group) versus 58.3% (modern group, p = 0.002), but mortality remained stable. No differences were observed in long-term survival. Centralization significantly increased the annual caseload. Improved preoperative workup enabled more accurate detection of locally advanced disease and subsequently appropriate multimodal treatment that is currently used in most patients. The ‘typical’ EC patient has shifted from the squamous cell to the adenocarcinoma type, but males are still more concerned. Postoperative complications are nowadays more rigorously detected and managed, keeping mortality rates low. Long-term survival remained unchanged over time.

Current perspectives of the Japanese Esophageal Oncology Group on the development of immunotherapy for esophageal cancer.

Esophageal cancer is the seventh most common cancer worldwide and continues to have a poor prognosis. Starting with the development of immune checkpoint inhibitors for patients with metastatic melanoma, many clinical trials have been conducted to evaluate the efficacy and safety of immune checkpoint inhibitors against various malignancies. Although few effective drugs are available for patients with advanced esophageal cancer, two immune checkpoint inhibitors, nivolumab and pembrolizumab, have been approved as second-line treatments for advanced esophageal squamous cell carcinoma. Recently, immune checkpoint inhibitors have shown promising results as post-operative therapies and first-line treatments for advanced esophageal cancer. Nivolumab has been approved as a post-operative therapy based on the CheckMate-577 trial, and nivolumab, ipilimumab and pembrolizumab have been approved as first-line treatments based on the CheckMate-648 trial and the KEYNOTE-590 trial. In addition, many trials of immune checkpoint inhibitors plus pre-operative treatment or definitive chemoradiotherapy are ongoing. The Japan Esophageal Oncology Group was established in 1978 and has conducted numerous clinical trials, most of which have examined multimodality treatments. In the era of immunotherapy, Japan Esophageal Oncology Group is conducting a clinical trial studying multimodality treatment with an immune checkpoint inhibitor. JCOG1804E (FRONTiER) is a phase I trial to evaluate the safety and efficacy of nivolumab plus pre-operative chemotherapy followed by surgery. These results might improve the clinical outcomes of esophageal cancer patients.

YAP1 acts as a negative regulator of pro-tumor TAZ expression in esophageal squamous cell carcinoma

PurposeAlthough YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive.MethodsFollowing single or double manipulation of YAP1 or TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We used RT-qPCR and Western blotting to examine their expression in the manipulated cells with or without inhibition of transcription or translation. We also examined the impact of YAP1 or TAZ deregulation on clinical outcome of esophageal cancer patients from the TCGA database.ResultsWe found that YAP1 functions as a tumor suppressor whereas TAZ exerts pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression.ConclusionFrom our data we conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.

Impact of Blood Parameters and Normal Tissue Dose on Treatment Outcome in Esophageal Cancer Patients Undergoing Neoadjuvant Radiochemotherapy.

Simple SummaryPrognosis of patients with locally advanced esophageal tumors remains poor despite ongoing efforts to improve treatment options. Nevertheless, neoadjuvant radiochemotherapy (RCTx) followed by surgery has resulted in increased survival rates. One critical point for irradiation of esophageal cancer is the optimal sparing of surrounding normal tissue, especially for the lungs, heart and bone marrow, in the immediate neighborhood of the target volume, since corresponding toxicity could impact the outcome of treated patients. Therefore, the aim of our study was to assess the potential influence of normal tissue radiation dose and blood parameters on survival in this patient cohort. Furthermore, functional imaging parameters of these organs at risk, extracted from 18F-FDG-PET/CT before and during neoadjuvant RCTx, have been correlated with the radiation dose to normal tissues and the blood parameters of interest. We found a significant association of higher radiation doses to the lungs and heart with overall survival. In contrast, neither functional imaging parameters nor blood values were prognostic in this neoadjuvant patient cohort.Despite technological advances, normal tissue sparing in photon beam irradiation is still challenging. Since in esophageal cancer this may inflict damage on the lungs, heart and bone marrow, possibly impacting on outcome, the aim of this study was to investigate the association of normal tissue dose and blood parameters on the survival of patients having undergone neoadjuvant radiochemotherapy (RCTx) followed by surgery. This retrospective study included 125 patients irradiated to 40–41.4 Gy with photons or protons combined with concurrent chemotherapy. On initial and restaging 18F-FDG-PET/CT, the lungs and heart were contoured as organs at risk for which standardized uptake values (SUV) were evaluated. The mean radiation dose (Dmean) to the lungs and heart, the volume of the lungs receiving at least 20 Gy (V20Gy_lung) and various pre- and per-treatment blood parameters were included in the Cox regression analyses. Results: The median follow-up time was 19.8 months and median overall survival 37 months (95% confidence interval: 16–58.9 months). In multivariate analysis, higher radiation doses to the lungs and heart were statistically significantly associated with decreased overall survival (Dmean_lung: p < 0.001; V20Gy_lung: p < 0.002; Dmean_heart: p = 0.005). Neither the 18F-FDG-PET nor blood parameters were predictive for overall survival. In patients with locally advanced esophageal cancer treated with RCTx, the radiation dose to the heart and lungs was significantly associated with overall survival.

Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]

Racial parity in esophageal cancer treatment at an integrated healthcare system.

e16105 Background: This study evaluates survival outcomes of esophageal cancer patients treated at a large, tertiary care integrated healthcare system and whether there are differences based on race. Methods: We conducted a retrospective study from January 2010 to December 2019 among patients at Kaiser Permanente Northern California (KPNC). Self-reported racial ethnic groups included Caucasian, African American, Hispanic, Asian, and Other. Kaplan Meier and Cox regression analyses were used to evaluate differences in race, age, stage, and treatment utilization in relation to overall survival. Results: A total of 1,692 patients were diagnosed with esophageal cancer. Of these, 11% were Asian, 8.1% were Hispanic, and 6% were African American. Caucasians had the oldest mean age at diagnosis, 70.2 years, and the Hispanics had the youngest mean age at diagnosis, 64.6 years (p &lt; 0.001). There were no statistically significant differences in stage at time of diagnosis between race groups (p = 0.41). Adenocarcinoma was more common in Caucasians and Hispanics, while squamous cell was more common in African Americans and Asians (p &lt; 0.001). Treatments received by the patients included, surgery, chemotherapy, radiation, and a combination thereof (multimodal). There was no statistical significance among the races in treatment modalities received, including multimodal therapy (p = 0.12-0.66). The difference in mean overall survival (OS) between the race groups was not statistically significant. Kaplan-Meier survival analyses were performed and demonstrated statistically significant differences in mean OS between the two histologies, with adenocarcinoma having the highest survival of 33.9 months (p &lt; 0.001). Conclusions: We identified racial parity in survival outcomes and treatment utilization for esophageal cancer patients who were treated at a large integrated healthcare system where patients have equal access to care.[Table: see text]

The Systemic Inflammation Score Is an Independent Prognostic Factor for Esophageal Cancer Patients who Receive Curative Treatment.

Perioperative systemic inflammation affects the long-term oncological outcomes in cases of malignancies. We evaluated the clinical impact of the preoperative systemic inflammation score (SIS) in resectable esophageal cancer patients who received curative treatment. This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Based on the 3- and 5-year OS rate, we set the cut-off value for SIS at 2 in the preset study. Among the 168 total patients, 119 were categorized as the Low-SIS group, and 49 were categorized as the High-SIS group. The respective 3- and 5-year OS rates were 61.9% and 52.4% in the Low-SIS group and 33.3% and 26.6% in the High-SIS group. There were significant differences in OS (p<0.001). The SIS was therefore selected for the final multivariate analysis model (hazard ratio=2.094, 95% confidence interval=1.355-3.234, p<0.001). On comparing the perioperative clinical course between the High- and Low-SIS groups, there were significant differences in the rate of postoperative anastomosis leakage of grade ≥2 between the groups (61.5% in the High-SIS group vs. 30.3% in the Low-SIS group; p=0.021). The systemic inflammation score had a clinical effect on the long-term oncological outcomes in esophageal cancer patients, suggesting that it might be a promising prognostic factor for esophageal cancer patients.

Usefulness of Prophylactic Administration of Pegfilgrastim for Esophageal Cancer Chemotherapy: A Single-center Retrospective Study.

To evaluate the impact of prophylactic administration of pegfilgrastim in esophageal cancer (EC) patients treated with chemotherapy consisted of docetaxel, cisplatin, and fluorouracil (DCF). Among 102 patients who received neoadjuvant or induction DCF for primary advanced EC, 65 received prophylactic pegfilgrastim and 37 did not. The association of pegfilgrastim with adverse events and clinicopathological outcomes was retrospectively analyzed. In the pegfilgrastim group, the incidence of grade >3 neutropenia was lower (30.8% vs. 62.2%) and more patients avoided dose reduction or discontinuation of chemotherapy (32.3% vs. 70.3%). The radiological (PR≤) and histopathological (grade 1b≤) response rates were significantly higher (69.2% vs. 43.2% and 59.2% vs. 35.7%). Three-year overall survival and progression-free survival rates were significantly higher (65.0% vs. 48.6%, p=0.033; 56.1% vs. 35.1%, p=0.007, respectively). Prophylactic pegfilgrastim in DCF may relieve adverse events and improve the oncologic outcome of EC patients.

Effectiveness of early exercise on reducing skeletal muscle loss during preoperative neoadjuvant chemotherapy for esophageal cancer.

To investigate if early exercise can help prevent skeletal muscle loss and improve the clinical outcomes of esophageal cancer patients receiving preoperative neoadjuvant chemotherapy (NAC). This was a single-center, retrospective observational cohort study of 110 patients with advanced esophageal cancer. We analyzed the effect of early exercise on the risk of skeletal muscle loss (defined as > 2.98%) during NAC and the subsequent clinical outcomes. Patients in the early exercise group (n = 71) started exercise therapy 8days earlier than those the late exercise group (n = 39). The median age of the patients was 65.4years, the mean BMI was 21.1kg/m2, and 92 (84%) of the 110 patients were men. Skeletal muscle loss occurred in 34% and 67% of the early and late exercise groups, respectively (p < 0.001). There was a lower risk of surgical site infection in the early exercise group (1% vs 16%, p = 0.021). Multivariate analysis revealed that early exercise reduced the risk of skeletal muscle loss (OR = 0.25, 95% CI 0.09-0.65, p = 0.006). Our results suggest that early exercise reduces the risk of both skeletal muscle loss during NAC and subsequent surgical site infection in patients with esophageal cancer.

Clinical Impact of Platelet-to-albumin Ratio on Esophageal Cancer Patients Who Receive Curative Treatment.

Perioperative nutrition and inflammation affect the oncological outcomes of various malignancies. We evaluated the clinical impact of the preoperative platelet-to-albumin ratio (PAR) in resectable esophageal cancer patients who received curative treatment. This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Based on the 3- and 5-year OS rates, we set the cut-off value for the PAR at 80×103 in the present study. Among 168 patients, 134 (79.8%) were defined as the PAR-low and 34 (20.2%) as the PAR-high group. The 3- and 5-year OS rates were 60.2% and 51.7% in the PAR-low group and 30.2% and 18.9% in the PAR-high group, respectively. There were significant differences in OS (p=0.005). The PAR was therefore selected for the final multivariate analysis model [hazard ratio=1.997, 95% confidence interval (CI)=1.230-3.241, p=0.037]. On comparing the perioperative clinical course between the PAR-high and PAR-low groups, there were marginally significant differences in the postoperative surgical complications and intraoperative blood loss between the groups. The PAR had clinical influence on the long-term oncological outcomes of esophageal cancer patients and might thus be a promising prognostic factor for esophageal cancer patients.

Disparities in esophageal cancer care based on race: a National Cancer Database analysis

Esophageal cancer is one of the most common cancer killers in our country. The effects of racial disparities on care for esophageal cancer patients are incompletely understood. Using the National Cancer Database, we investigated racial disparities in treatment and outcome of esophageal cancer patients. The National Cancer Database was queried from 2004 to 2017. Logistic regression and survival analysis were used to determine racial differences in access, treatment and outcome. A total of 127,098 patients were included. All minority groups were more likely to be diagnosed at advanced stages versus Caucasians after adjusting for covariates (African American OR-1.64 [95% confidence interval 1.53-1.76], Hispanic OR-1.19 [1.08-1.32], Asian OR-1.78 [1.55-2.06]). After adjustment, all minorities were less likely at every stage to receive surgery. Despite these disparities, Hispanics and Asians had improved survival compared with Caucasians. African Americans had worse survival. Racial disparities for receiving surgery were present in both academic and community institutions, and at high-volume and low-volume institutions. Surgery partially mediated the survival difference between African Americans and Caucasians (HR-1.13 [1.10-1.16] and HR-1.04 [1.02-1.07], without and with adjustment of surgery).There are racial disparities in the treatment of esophageal cancer. Despite these disparities, Hispanics and Asians have improved overall survival versus Caucasians. African Americans have the worst overall survival. Racial disparities likely affect outcome in esophageal cancer. But other factors, such as epigenetics and tumor biology, may correlate more strongly with outcome for patients with esophageal cancer.

Perioperative Outcomes After Combined Esophagectomy and Lung Resection

The impact of concomitant lung resection during esophagectomy on short-term outcomes is not well characterized. This study tests the hypothesis that lung resection at the time of esophagectomy is not associated with increased perioperative morbidity or mortality. Perioperative outcomes for esophageal cancer patients who underwent esophagectomy alone (EA) were compared to patients who had concurrent esophagectomy and lung resection (EL) using the NSQIP database between 2006-2017. Predictors of morbidity and mortality, including combined surgery, were evaluated using multivariable logistic regression. Among the 6,225 study patients, 6,068 (97.5%) underwent EA and 157 (2.5%) underwent EL. There were no differences in baseline characteristics between the two groups. Operating time for EL was longer than EA (median 416 versus 371 minutes, P < 0.01). Median length of stay was 10 d for both groups. Perioperative mortality was not significantly different between EL and EA patients (5.1% versus 2.8%, P=0.08). EL patients had higher rates of postoperative pneumonia (22.3% versus 16.2%, P=0.04) and sepsis (11.5% versus 7.1%, P=0.03), however major complication rates overall were similar (40.8% versus 35.3%, P=0.16). Combining lung resection with esophagectomy was not independently associated with increased postoperative morbidity (AOR 1.21 [95% CI 0.87-1.69]) or mortality (AOR 1.63 [95% CI 0.74-3.58]). Concurrent lung resection during esophagectomy is not associated with increased mortality or overall morbidity, but is associated with higher rates of pneumonia beyond esophagectomy alone. Surgeons considering combined lung resection with esophagectomy should carefully evaluate the patient's risk for pulmonary complications and pursue interventions preoperatively to optimize respiratory function.

Comparison of Postoperative Esophagectomy Outcomes in Esophageal Cancer Patients Receiving Preoperative Radiotherapy at an Academic Medical Center vs. Community Medical Centers

Treatment for locally-advanced esophageal cancer commonly involves upfront radiotherapy and chemotherapy prior to surgery. Esophagectomy is a complex oncologic procedure that results in lower perioperative morbidity and mortality when performed in high-volume hospitals by experienced surgeons. Radiotherapy is a critical component of management and can lead to both acute and chronic local toxicity that directly impacts risk of surgical complications. Limited data exists evaluating the importance of radiation delivery at high vs low volume centers. We sought to compare postoperative toxicity amongst patients treated with preoperative radiotherapy delivered at an academic medical center (AMC) versus community medical centers (CMC).Consecutive patients undergoing esophagectomy for locally-advanced esophageal or gastroesophageal junction (GEJ) cancer at an academic medical center between 2008 and 2018 were reviewed. Patients treated for stage IVB or recurrence were excluded as were patients with incomplete treatment details. All patients were treated with intensity modulated radiation therapy (IMRT) or 3D conformal radiation therapy (3D CRT). Rural-Urban Continuum Codes were assigned to patients' residential addresses. Differences between groups were compared using chi-squared or t-tests.148 consecutive patients were identified: 89 CMC and 59 AMC. Median follow up was 30 months (0.33-124 months). Most patients were male (85.8%) with adenocarcinoma (90%) located in the distal esophagus or GEJ (95%). Distance between residential address and surgery center differed between groups (78 miles CMC vs 41 miles AMC, P < 0.01) with a trend towards more rural patients from CMCs (28% vs 15%, P = 0.07). AMC patients consisted of more women (25.4% vs 6.7%, P < 0.01) otherwise groups were balanced. The median time to surgery in CMC was 51 days and 49 days for AMC. Median radiation dose was 50.4 Gy (39.6 - 61.2 Gy) for CMC and 50.4 Gy (41.4 - 56 Gy) for AMC (P = 0.60). IMRT was more commonly used in CMCs than AMCs (66% vs 41%, P < 0.01). No difference between AMC and CMC was observed when comparing length of hospitalization, 90-day readmission rate, or wound, pulmonary or cardiac complications. Radiotherapy at CMCs required higher rates of re-operation after esophagectomy (19% vs 7%, P = 0.03). Anastomotic leak occurred in 38% CMC patients compared to 17% AMC patients (P < 0.01). Overall anastomotic stenosis rates were higher among CMC patients compared to AMC (35% vs 16%, P = 0.01) with a median time to stenosis of 2.8 months.Esophageal cancer patients receiving preoperative radiotherapy had higher rates of postoperative toxicity when radiotherapy was completed at a community medical center versus academic medical center. Explanations for these differences are uncertain but further exploratory analyses regarding dosimetry and radiation field size are warranted.

The impact of lymphopenia during chemoradiotherapy using photons or protons on the clinical outcomes of esophageal cancer patients.

We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose-volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5-50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.

High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients.

Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring.

Impact of Frailty on Treatment Outcome in Patients With Locally Advanced Esophageal Cancer Undergoing Concurrent Chemoradiotherapy

The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT). Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival. A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046]. Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.