Locoregional Esophageal Cancer Research Articles

Do socioeconomic factors impair uptake of neoadjuvant therapy for patients with locoregional oesophageal cancer?

The benefits of neoadjuvant therapy prior to surgery for patients with locally advanced oesophageal cancer have been well established by multiple trials. However, there may be socioeconomic barriers impacting equitable administration. We aim to identify whether disparities exist in uptake of neoadjuvant therapy among patients with loco-regional oesophageal cancer. We queried the National Cancer Database, identifying patients with clinical stage II-III oesophageal cancer who underwent surgical resection (2006-2020). Logistic regression was performed to identify associations between sociodemographic factors and uptake of neoadjuvant therapy. In propensity score-matched groups, survival was evaluated using the Kaplan-Meier method. Among 19,748 clinical stage II-III patients, 85% (n = 16,781) received neoadjuvant therapy and 15% (n = 2,967) underwent upfront surgery. Rates of neoadjuvant uptake increased over time. On multivariable analysis after adjusting by clinical stage, factors associated with lower rates of neoadjuvant therapy included older age (age ≥70, adjusted odds ratio 0.52; 95% Confidence Interval 0.47-0.57; p < 0.001), female sex (0.76; 0.69-0.85; p < 0.001), Black race (0.77; 0.63-0.94; p = 0.009), more comorbidities (0.76; 0.65-0.85; p < 0.001), and government rather than private insurance (0.84; 0.76-0.93; p < 0.001). In a propensity-matched cohort accounting for these variables, neoadjuvant treatment was associated with improved 5-year overall survival compared to upfront surgery (41.1%vs.35.4%,p < 0.001). Several sociodemographic factors are associated with the delivery of neoadjuvant therapy in patients with oesophageal cancer, including age, sex, race, and insurance status. Interventions can be put into place to target vulnerable patients and ensure equitable delivery of care.

Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study

BackgroundAdjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.MethodsThis phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.ResultsTwenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7–33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0–19.5) and 21.6 (95% CI: 0.0–45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.ConclusionsAdjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC.Trial registration number ClinicalTrials.gov (No. NCT03322267).

Neoadjuvant nivolumab plus paclitaxel/cisplatin- chemo-radiotherapy (neo-NTP-CRT) followed by esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II study.

e16098 Background: Adjuvant nivolumab has shown efficacy in reducing recurrence in patients (pts) with locoregional esophageal cancer harboring pathologic residual disease following neoadjuvant chemoradiotherapy (CRT). However, the efficacy of adding nivolumab to neoadjuvant CRT remains unclear. Methods: We conducted a phase II trial of neoadjuvant nivolumab (240mg IV on D-14, 1, 15, 29), paclitaxel (50mg/m2 IV on D1, 8, 15, 22, 29), cisplatin (30mg/m2 IV on D1, 8, 15, 22, 29) and RT (45Gy given in 25 fractions) followed by esophagectomy 6 to 8 weeks after finishing CRT in pts with locally advanced ESCC, defined as clinical stage cT3-4aN0M0 or cT1-3N1-3M0 according to the AJCC Cancer Staging System 8th ed. (ClinicalTrials.gov Identifier: NCT05130684). The study, in a Simon’s two-stage design, used pathological complete response (pCR) rate as the primary endpoint. Secondary endpoints included feasibility, safety, recurrence free survival (RFS), progression free survival (PFS), and overall survival (OS). Results: Between Jan 2021 and Apr 2023, we enrolled a total of 17 pts. Fifteen were male. The median age was 52 years (range: 44~69). The clinical stage was I, II, and III in 1, 1, and 15 pts, respectively. All pts received neo-NTP-CRT with the following dose-intensities (mean dose intensity [range]): nivolumab (95% [50%~ 100%]), paclitaxel (75% [48%~ 100%], cisplatin (97% [80%~ 100%]), and radiotherapy (100%). Fourteen pts received esophagectomy, and 4 of them achieved pCR (24%). Because pCR for the first stage did not meet the efficacy criteria to move forward to second-stage, the enrollment was discontinued after enrolling 17 pts. During neo-NTP-CRT, the most common treatment-related adverse events (TRAEs) were leukopenia (76%), neutropenia (59%), thrombocytopenia (35%), and skin rash (35%); and the most common grade 3 and 4 TRAEs were leukopenia (24%), neutropenia (6%), and nausea and vomiting (6%). Among 14 pts receiving esophagectomy, 4 experienced surgical complications, including 2 with anastomotic leakage, 1 with subclavian artery rupture, and 1 with pneumonitis; one pt died 263 days after surgery, followed by a prolonged hospital stay due to refractory anastomotic leakage, infectious complications, and tumor progression. The median follow-up duration was 18 months. Median RFS, PFS and OS was 8, 12, and 16 months, respectively. Conclusions: Our data indicate that adding nivolumab to neoadjuvant paclitaxel and cisplatin-based CRT is feasible but does not improve pCR rate in locally advanced ESCC pts. Clinical trial information: NCT05130684 .

Adjuvant chemoradiotherapy (CRT) plus pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC) with high risk of recurrence after neoadjuvant CRT plus surgery: A single-arm phase II study.

320 Background: Adjuvant anti-PD-1 therapy with nivolumab has shown efficacy in reducing recurrence rates in patients with locoregional esophageal cancer including squamous cell carcinoma who achieved R0 resection but harboring pathologic residual disease following neoadjuvant CRT. However, the efficacy of adjuvant anti-PD-1 therapy in improving outcomes for patients at higher risk of recurrence, especially those with involved or close resection margin (≤1 mm), remains unclear. Methods: We conducted a phase II trial of adjuvant cisplatin (30mg/m2 IV every week for 2 cycles)-based CRT (180-200cGy per fraction for 10-13 fractions) followed by pembrolizumab (200mg IV every 3 weeks for 18 cycles) in patients with locally advanced ESCC who had high-risk recurrence features in esophagectomy tumor tissues, including involved or close margin (≤1 mm), extranodal extension (ENE) of involved lymph node, and ypN2-3, following neoadjuvant CRT (ClinicalTrials.gov Identifier: NCT03322267). Primary endpoint was 1-year relapse-free survival (RFS) rate in comparison with a historical control of 32%.1 Secondary endpoints included RFS, overall survival (OS), and toxicity. Results: Between Nov 2018 and Dec 2022, we enrolled a total of 25 patients with high risk recurrence features, including margin ≤1 mm (18 patients), ENE of involved lymph node (9), and ypN2-3 (9). Majority of patients were male (88%) and current smokers (84%). The median follow-up duration was 16.5 months (95% CI 10.6-27.1). One-year RFS rate was 63.3% (95% CI 44.5-79.8). Median RFS and OS were 15.3 months (95% CI 10.2-20.4) and 38.3 months (95% CI 10.2-66.3), respectively. Any grade treatment emergent adverse events (TEAEs) occurred in 56% and 75% of patients during cisplatin-based CRT and pembrolizumab treatment, respectively. Grade 3 TEAEs were infrequent, including leukopenia (4%), pancreatitis (4%), infection (8%), and colitis (4%). There was no grade 4 TRAE. Conclusions: Adjuvant cisplatin-based CRT followed by 1-year treatment of pembrolizumab was well-tolerated, and was associated with an improved 1-year RFS rate in patients with pathologic residual disease and high risk for recurrence following trimodality therapy for locally advanced ESCC. 1. Guo JC et al: J Thorac Oncol 2015;10:1481-9. Clinical trial information: NCT03322267 .

472. STATEWIDE TRENDS IN ESOPHAGECTOMY APPROACH: DATA FROM A REGIONAL THORACIC QUALITY COLLABORATIVE

Abstract Background Esophagectomy patients continue to have high morbidity and mortality. Regional quality collaboratives have been shown to improve care around cardiac surgery. Our statewide cardiac surgery collaborative (33 programs) created thoracic surgery collaborative 10 years ago, sharing data to improve care at all locations. There were 17 programs participating in sharing lung cancer surgery data, and 10 programs sharing esophageal cancer surgery data. We reviewed trends in esophagectomy approach and perioperative outcomes from the quality collaborative. Methods Prospectively collected data from patients with loco-regional esophageal cancer who underwent esophagectomy between 2014 to 2022 were analyzed. We evaluated 3 separate 3-year cohorts. Pre-operative assessment, surgical approach lymph node harvest, post-operative outcomes, and length of stay (LOS) were analyzed using linear regression and chi squared tests. Results Annual esophagectomy volume ranged from 114 to 145 cases per year. There was significant increase in use of preoperative CT scans (p = 0.02) and a trend towards higher use of endoscopic resection as part of the staging paradigm (p = NS). There was a notable shift towards more minimally invasive esophagectomy approaches (p &amp;lt; 0.0001) with robotic assisted minimally invasive esophagectomy being the most common in the recent cohort (Figure). Lymph node harvest trended towards higher yield over time, but was only significant with the open trans-thoracic approaches (p &amp;lt; 0.01). There were no significant differences noted in rates of positive margin or in length of stay. Conclusion Regional quality collaboratives allow for tracking of esophageal cancer care at a broader level than single institutions. We noted increased use of minimally invasive techniques, specifically robotic assisted over the past decade with trends towards improved lymph node dissection. Despite the increase use of minimally invasive surgery, length of stay did not change.

375. RURAL PATIENTS HAVE A PROLONGED INPATIENT RECOVERY PROCESS AFTER ESOPHAGECTOMY COMPARED TO NON-RURAL PATIENTS AT A HIGH-VOLUME ESOPHAGEAL PROGRAM

Abstract Background Geographic access to care plays a large role in health disparities in esophageal cancer care, with rural individuals often travelling further to access complex healthcare services. We sought to characterize peri-operative outcomes in patients undergoing esophagectomy for loco-regional cancer at a single academic tertiary care center based on geographic home location. We hypothesize that rural patients will have worse peri-operative outcomes after esophagectomy, despite receiving care at the same high-volume hospital. Methods Prospectively collected data from patients with loco-regional esophageal cancer who underwent esophagectomy at a single academic medical center between 2003 to 2022 were analyzed based on county. The counties were aggregated into previously existing state-level ‘metropolitan’ versus ‘rural’ designations per the Rural Health Information Hub guidelines. Distance traveled by the patients were calculated using driving distance between the patient’s reported zip code and hospital address. Demographics, pre-operative treatment, surgical complications, post-operative outcomes, length of stay (LOS), and mortality of the two groups were analyzed using chi-squared, paired t-tests, and single-factor ANOVA. Results The cohort consisted of 1545 patients with 76.0% from metropolitan counties and 24.0% from rural counties. Patients were more likely to be male in both groups (p = 0.004), with no significant differences in pre-operative characteristics. Both groups had similar rates of pre-operative chemotherapy (p = 0.11) and pre-operative radiation (p = 0.58). Rural patients traveled greater distances for healthcare services compared to metropolitan patients (rural: 192.4 ± 101.2 miles; metropolitan: 63.4 ± 36.7 miles; p &amp;lt; 0.001). Post-operatively rural patients had higher rates of pneumonia (p = 0.04) and more initial ICU visits (p &amp;lt; 0.001). Rural patients had longer ICU LOS (p &amp;lt; 0.001), but no difference in total hospital LOS (p = 0.28) or 30-day mortality (p = 0.35). Conclusion Rural patients tended to have a more complex inpatient recovery process after esophagectomy despite receiving surgery at the same high-volume institution and no differences in pre-operative characteristics (BMI, smoking history, and co-morbidities). It is unclear as to the reason for differences in pneumonia rates and ICU stays. Future studies should focus on the impact of rural location on disparities for individuals undergoing esophagectomy.

283. 18F-FDG PET/MRI FOR RESTAGING ESOPHAGEAL CANCER AFTER NEOADJUVANT CHEMORADIOTHERAPY

Abstract Background The accuracy of 18F-FDG PET/CT is insufficient to detect residual locoregional esophageal cancer after neoadjuvant chemoradiotherapy (nCRT). This feasibility study aims to investigate whether post-treatment 18F-FDG PET/MRI may potentially improve tumor detection. Methods This was a prospective, single center feasibility study. At 6–12 weeks after nCRT, patients underwent standard 18F-FDG PET/CT followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18F-FDG PET/CT or the 18F-FDG PET/MRI first; the other scan was assessed one month later. SULmax and ADCmean were measured at the primary tumor location. Histopathology of the surgical resection specimen served as reference standard for diagnostic accuracy calculations. When patients with clinically complete response continued active surveillance, response evaluations until nine months after nCRT served as proxy for ypT and ypN (i.e. ‘ycT’, ‘ycN’). Results In the 21 included patients (median age 70 [IQR 62–75], 16 males), disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans), and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18F-FDG PET/MRI vs 18F-FDG PET/CT was 38/57% vs 76/61%. For ypN+, accuracy was 63/53% vs 63/42%, resp. Neither SULmax (both scans) nor ADCmean were discriminatory for yp/ycT+. Fourteen of 21 (67%) patients were willing to undergo a similar 18F-FDG PET/MRI examination in the future. Conclusion 18F-FDG PET/MRI currently performs comparably to 18F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience, and performing serial scans might contribute to enhance accuracy of tumor detection after nCRT using 18F-FDG PET/MRI.

Comparison of different neoadjuvant treatments for resectable locoregional esophageal cancer: A systematic review and network meta-analysis.

PurposeThe best pattern of neoadjuvant therapy for resectable locoregional esophageal cancer has not been determined. Our study evaluated the efficacy and postoperative events of different treatments using the Bayesian network meta‐analysis.MethodsWe systematically tracked randomized clinical trials from the Medline, EMBASE, and Cochrane Library databases. The following treatments were included: neoadjuvant chemoradiation followed by surgery (NCRT + S), neoadjuvant chemotherapy followed by surgery (NCT + S), neoadjuvant radiotherapy followed by surgery (NRT + S), and surgery alone (S). The Revised Cochrane risk‐of‐bias tools were used to assess the quality of included trials. Overall survival (OS) and progression‐free survival or disease‐free survival (PFS/DFS) were assessed through hazard ratios (HR). Locoregional recurrence, distant metastasis, postoperative mortality, and postoperative morbidity were assessed through odds ratios (OR). These outcomes were compared between different treatments through Bayesian network meta‐analysis.ResultsTwenty trials with 4384 patients were included. Compared with S, only NCRT + S could significantly improve OS for patients with esophageal cancer (HR = 0.78, 95% confidence interval [CI] 0.68–0.88). NCRT + S and NCT + S significantly improved PFS/DFS compared with S (NCRT + S vs. S, HR = 0.72, 95% CI 0.63–0.81; NCT + S vs. S, HR = 0.81, 95% CI 0.69–0.97). NCRT + S significantly reduced both locoregional recurrence (OR = 0.67, 95% CI 0.51–0.88) and distant metastasis (OR = 0.63, 95% CI 0.45–0.90) compared with S. There were no differences in postoperative morbidity between the four treatments. However, NCRT + S also increased postoperative mortality compared with S (OR = 1.77, 95% CI 1.09–2.82) and NCT + S (OR = 1.96, 95% CI 1.11–3.51).ConclusionNCRT + S is the most efficient neoadjuvant treatment for resectable locoregional esophageal cancer. However, NCRT + S increases the risk of postoperative mortality but not morbidity.

The effect of histologic grade on neoadjuvant treatment outcomes in esophageal cancer.

The gold standard for locoregional esophageal cancer (LEC) treatment includes preoperative chemoradiation and surgical resection, with possible perioperative or adjuvant systemic therapy. With few data associating histologic grade and prognosis in LEC patients receiving neoadjuvant chemoradiation followed by resection, we seek to evaluate this association. Our institutional esophagectomy database between 1999 and 2019 was queried, selecting esophageal adenocarcinoma patients who completed neoadjuvant therapy (NAT), followed by esophagectomy. Propensity-score matching of low- and high-histologic grade groups was performed to assess survival metrics using initial clinical grade (cG) and final pathologic grade (pG). We performed a multivariable logistic regression to study predictors of pathologic complete response as a secondary objective. A total of 518 patients met the inclusion criteria. Kaplan-Meier analysis of the matched dataset showed no difference in initial or 5-year recurrence-free survival or overall survival (OS) between cG1 and cG2 versus cG3 based on original grade. When matched according to pG, cG1-2 had improved median survival parameters compared to cG3, with 5-year OS for cG1-2 of 45% versus 27% (p = 0.001). Higher pG, pathologic N stage, and poor response to NAT are predictors of poor survival. Patients with post-NAT pG1-2 demonstrated improved survival. Integrating histologic grade into postneoadjuvant staging may be warranted.

Assessment of changes in chest wall mechanics in esophageal cancer survivors using a 3D-motion capture system.

TPS360 Background: Surgical resection remains the mainstay of treatment for loco-regional esophageal cancer. Traditional open esophagectomy is associated with considerable morbidity, with postoperative pulmonary complications (PPC) being the most frequently observed morbidity. There are several peri- and postoperative factors that are known to affect the respiratory mechanics, including an open surgical approach, administration of sedatives, rib spreading with subsequent fracture or nerve injury, presence of PPC and neuropathic pain leading to post-thoracotomy syndrome. Enhanced recovery programmes with early mobilization protocols and chest physiotherapy have been shown to reduce pulmonary complication rates. However, no data is currently available regarding the long-term respiratory function, quality of life and chest wall function in esophageal cancer survivors. Quantification of chest wall movements provides an objective measurement of function for the long term assessment of chest wall mechanics and could be used to develop tailored physiotherapy for patients undergoing esophagectomy. The aim of this study is to develop a method to objectively quantify changes in breathing mechanics in esophageal cancer survivors using a biomechanical approach. Methods: In the initial phase, an 89-marker protocol will be validated against a 3D-printed chest wall model that can produced simulate of normal and abnormal motions. Retroreflective markers will be placed non-invasively on the anterior, posterior, and lateral parts of the thorax and abdomen. A working protocol of breathing mechanics will be assessed in healthy control volunteers with the subject seated in upright position. Subjects will perform the respiratory function tests, the spirometer and the respiratory pressure meter. Further to this clinical assessment, the impact of thoracic movements and treadmill exercise will be assessed on the parameters obtained from changes in breathing movements. Following this, an optimization phase will refine markers placement and identify parameters that are most likely to be clinically relevant in the assessment of breathing mechanics. A finalized protocol will be trialled in esophageal cancer survivors, to identify changes in thoracoabdominal motion after surgery and to assess whether these changes are associated with impairment in health-related quality of life. This information will aid the development of evidenced based physiotherapy regimens tailored to the needs of this patient population. Clinical trial information: NCT03835273.

Evolving treatment paradigms in esophageal cancer.

A heterogenous disease with a dismal prognosis, esophageal cancer poses a major health challenge worldwide. In recent years, the treatment landscape for esophageal adenocarcinoma and squamous cell carcinoma (SCC) has undergone major evolution, with the elucidation of underlying biologic pathways and predispositions. Neoadjuvant chemoradiation has emerged as a leading approach for the management of locoregional esophageal cancer, while perioperative chemotherapy has shown promising outcomes specifically in adenocarcinoma of the lower esophagus and gastroesophageal junction (GEJ). Studies also explore the implementation of chemoradiation in various sequential preoperative strategies, as well as in the adjuvant setting. Definitive chemoradiation is considered a valid alternative for non-surgical candidates with SCC. Clinical trials currently evaluating the potential benefits of different approaches may shed light on existing controversies regarding optimal management of locoregional disease. For patients with metastatic cancer, chemotherapy remains the backbone of antineoplastic treatment alongside palliative care, moreover the discovery of novel biological targets has led to the initiation of targeted and immune therapy for specific subpopulations. Taken together, an era of burgeoning clinical trials and changing paradigms has evolved in esophageal oncology. Multidisciplinary collaboration is key to effective combination and sequencing of treatment modalities tailored per patient and per tumor histology. This work aims to provide a comprehensive overview of state-of-the-art oncological management of esophageal cancer, with consideration of new challenges and obstacles to be overcome.

15-Year Experience with Multimodality Therapy Including Esophagectomy for Elderly Patients with Locoregional Esophageal Cancer

Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population. Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger." One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS). Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients.

The effect of gender on outcomes in esophageal cancer.

170 Background: Few epidemiological studies address differences in outcomes by gender in locoregional esophageal cancer (LEC) for which the current standard of care is chemoradiation followed by surgical resection. Although male gender is associated with the majority of LEC cases, we sought to determine if gender could impact clinical presentation as well as surgical and oncologic outcomes in our single institution 20 year experience. Methods: A retrospective query of our institution’s IRB-approved database of patients that had surgical therapy between 2008 and 2019 for esophageal cancer (EC) was performed. Patients were stratified by gender and analyzed based on characteristics such as tumor histology, tumor location, clinical stage at presentation, age at diagnosis, receipt of neoadjuvant therapy, surgical intent, surgical complications, length of post-operative hospital stay, response to neoadjuvant therapy, final pathology, and recurrence. Chi-square, ANOVA and Kaplan Meier survival analysis were performed on the previously defined groups. Results: The cohort studied included 1180 patients with resection for EC. Of those, 1005 (85.2%) had adenocarcinoma, 145 (12.3%) had squamous cell cancer (SCC), 10 (0.8%) had adenosquamous carcinoma, and 20 (1.7%) had other histological variants. There were 985 (83.5%) male patients and 195 (16.5%) female patients. SCC was more common in females (29.2% in females vs. 8.9% in males, p = 0.000) and females tended to have tumor location in the upper thoracic esophagus more often (4.7% in females vs. 0.9% of males, p = 0.000). Additionally, females developed surgical complications more often than males (72.2% vs. 64.7%, p = 0.045). Staging at diagnosis (p = 0.508), receipt of neoadjuvant treatment (p = 0.676), and age at diagnosis (65.3 years in males vs. 66.3 years in females, p = 0.934) had no association with gender. Response to neoadjuvant therapy (p = 0.157) and cancer recurrence (p = 0.434) did not have significant associations with gender. The median overall survival was not statistically significantly different but trended to be longer for females (73.4 months in females [95% CI: 51.5-95.4] vs. 47.0 months in males [95% CI: 39.6-54.5], p = 0.160). Conclusions: Based on our high-volume cancer center study, female patients were more likely to have SCC, upper thoracic esophageal lesions, and surgical complications following resection. While univariate analysis did not demonstrate significant differences in overall survival between genders, there are plans to report additional data after controlling for other variables. Further studies are warranted to validate these findings, given the potential for higher prioritization of an organ preservation approach for this patient population.

Comparation of Different Neoadjuvant Treatments for Resectable Locoregional Esophageal Cancer – A Systematic Review and Network Meta-Analysis (NMA)

Neoadjuvant treatments have been one of the most common patterns in resectable locoregional esophageal cancer. Our study is to evaluate the effect of different neoadjuvant treatments for esophageal cancer and determine the best pattern of treatment by using the Bayesian NMA. We systematically tracked eligible data from Medline, EMBASE, CENTRAL and clinical trials database. The following treatments were included: neoadjuvant chemoradiation followed by surgery (NCRT+S), neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant radiotherapy followed by surgery (NRT+S) and surgery alone (S). The other inclusion criterion included full-test available research and prospective randomized clinical trials. Trials on minority or with treatments which were off-standard such as low radiotherapy dose were excluded. Hazard Ratios (HR) were extracted from the text or calculated from Kaplan- Meier curve and then pooled to compare the effect on overall survival (OS). 4107 patients from 18 trials were enrolled in the final analysis. There were 4 groups: NCRT+S (1198), NCT+S (1140), NRT+S (48) and S alone (1821). Ranking analysis showed that the best treatment was NCRT+S, with a SUCRA score of 0.81, compared with NCT+S of 0.70, NRT+S of 0.37 and S of 0.12. The result of NMA on relative effect was shown in table 1. Only NCRT+S could significantly improve OS compared with S (direct HR 0.77, 95%CI 0.65-0.91; indirect HR 0.76, 95%CI 0.51-1.11; network HR 0.77, 95%CI 0.65-0.90). NRT+S and NCT+S seemed to be superior to S, but the difference was not significant. When comparing the three neoadjuvant groups, NCRT+S and NRT+S reached a same level of hazard and both were superior to NCT+S, but no significant difference was observed among the three groups: NCRT+S vs NCT+S HR = 0.84, 95%CI 0.66-1.02; NCRT vs NRT+S HR = 1 95%CI 0.57-1.78; NCT+S vs NRT+S HR = 1.17 95%CI 0.67-2.11. NCRT+S seems to be the best treatment model for resectable locoregional esophageal cancer. But more evidence is still needed to show the advantage of NCRT+S when comparing with NCT+S or NRT+S. Table 1 Results of relative effect for the 4 treatmentsAbstract 3412; TableNCRT+SNCT+SNRT+SSNCRT+SNCRT+S1.20 (0.98-1.51)1 (0.56-1.75)1.3 (1.11-1.54)NCT+S0.84 (0.66-1.02)NCT+S0.86 (0.47-1.5)1.09 (0.9-1.28)NRT+S1 (0.57-1.78)1.17 (0.67-2.11)NRT+S1.32 (0.74-2.44)S0.77 (0.65-0.9)0.92 (0.78-1.12)0.76 (0.41-1.35)S Open table in a new tab

Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

326 DEFINITIVE CHEMORADIOTHERAPY COMPARED TO NEOADJUVANT CHEMORADIOTHERAPY WITH ESOPHAGECTOMY FOR LOCO-REGIONAL ESOPHAGEAL CANCER: NATIONAL POPULATION-BASED COHORT STUDY

Abstract Ongoing randomized controlled trials seek to evaluate the potential organ-preservation strategy of definitive chemoradiotherapy as a primary treatment for esophageal cancer. This population-based cohort study aimed to assess survival following definitive chemoradiotherapy (DCR) with or without salvage esophagectomy (SALV) in the treatment of esophageal cancer. Methods Data from the National Cancer Database (NCDB) from 2004 to 2015, was used to identify patients with non-metastatic esophageal cancer receiving either DCR (n = 5,977) or neoadjuvant chemoradiotherapy with planned esophagectomy (NCRS) (n = 13,555). Propensity score matching (PSM) and multivariable analyses were used to account for treatment selection bias. Subset analyses compared patients receiving salvage esophagectomy after DCR (SALV) with NCRS. Results Comparison of baseline demographics of the unmatched cohort revealed that patients receiving NCRS were younger, had a lower burden of medical comorbidities, lower proportion of squamous cell carcinoma (SCC) and more positive lymph nodes. Following matching, NCRS was associated with significantly improved survival compared with DCR (HR: 0.60, 95% Confidence Interval (CI): 0.57—0.63, p &amp;lt; 0.001), which persisted in subset analyses of patients with adenocarcinoma (HR: 0.60, 95%CI: 0.56—0.63, p &amp;lt; 0.001) and SCC (HR: 0.58, 95%CI: 0.53—0.63, p &amp;lt; 0.001). There was no difference in overall survival between SALV and NCRS (HR: 1.00, 95%CI: 0.90—1.11, p = 1.0). Conclusion Surgery remains an integral component of the management of patients with esophageal cancer. Neoadjuvant therapy followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with loco-regional esophageal cancer.

Mean Cardiopulmonary Dose and Vertebral Marrow Dose Differentially Predict Lineage-Specific Cytopenia Kinetics During Radiotherapy for Esophageal Cancer

Lymphopenia is associated with poor outcomes in esophageal cancer (EC) patients (pts) undergoing chemoradiotherapy (CRT). While dose to vertebral marrow is implicated in lymphopenia, cytopenic effects of RT on non-marrow compartments are not well described. We hypothesized that dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) has unique effects on WBC counts and clinical outcomes. We identified clinical and dosimetric factors associated with cytopenias in EC pts undergoing CRT, and temporally characterized dose-dependent effects on central and peripheral hematological compartments during therapy. Weekly and 90-day post-CRT cell counts (lymphocyte [Lym], neutrophil [Neu], hemoglobin [Hgb], and platelet [Plt]) were retrospectively collected for 49 pts treated with CRT (definitive or neoadjuvant) for locoregional EC. Dose volume histogram data for thoracic vertebral (TV) volumes receiving 10-40 Gy (TV10-4010-40 Gy (TVS10-40 Gy) was calculated by subtracting TV10-TV40 from total TV volume. Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels, excluding marrow, as a surrogate for circulating blood pool. We used linear and logistic regression to examine associations between absolute (Abs) and normalized (Nml) cell count nadirs and grade 3 (Gr3) and 4 (Gr4) cell count toxicities by CTCAE v5.0. Repeated measures ANOVA tested for associations between cell count trends and clinical predictors. WBC and Plt counts reached nadir at week 6 of CRT and Hgb at 90 days post-CRT. Abs WBC and Nml Lym declined more rapidly in diabetic pts (p=.02, p=.05); Nml Lym also declined more rapidly with age >66 (p=.047). mCPD was strongly associated with lower Abs and Nml WBC nadir (p=.0003, p=.0006), and Abs and Nml Neu nadir (p<0.01, p=.02), but not Lym nadirs (p>.27). In contrast, TVS10-30 and TV10-20 were associated with Abs Lym nadir (all p<.03, p≤.01) and Nml Lym nadir (all p≤.01, all p≤.001). mCPD was associated with Gr3+ leukopenia (p=.04) and Gr3+ neutropenia (p=0.01). In multivariate analysis, mCPD remained associated with Abs WBC nadir (p=.0018) Nml Neu nadir (p=.0392) and Abs Neu nadir (p=.0053), and TVS10-40 remained associated with Nml Lym nadir (all p≤.042). Mean cardiopulmonary dose and TV marrow dose differentially predict lineage-specific cytopenias during CRT for EC. mCPD is significantly associated with lower Abs and Nml nadirs of multiple cell lines, with the exception of Lym. In contrast, TV dose is significantly associated with lower Lym nadirs but not with other cytopenias. Diabetes and age are associated with a more rapid decline in WBC and Lym counts. Further studies are needed to confirm mechanisms of mCPD-associated count suppression, and to prospectively evaluate the influence of these factors on pt outcomes.

Racial Disparities, Outcomes, and Surgical Utilization among Hispanics with Esophageal Cancer: A Surveillance, Epidemiology, and End Results Program Database Analysis

Background: Hispanic patients with esophageal cancer (EC) have racially disparate survival outcomes compared with white patients. Objectives:We explored the impact on survival of racial differences in socioeconomic factors, tumor characteristics, and rates of surgical utilization in patients with EC. Method:Using the SEER (Surveillance, Epidemiology, and End Results) registry, we identified 22,531 cases of EC in Hispanic and white patients between the ages of 18 and 65 years in 2003–2014. Of these, 6,250 cases had locoregional EC. Patients were categorized according to age, gender, education, tumor grade, histology, primary tumor site, and surgical status. Postdiagnosis survival was examined over time and compared by race and stratified by surgical status. Results: Compared with whites, Hispanics with EC had significantly higher unadjusted mortality (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.06–1.17; p < 0.001) as did Hispanics with locoregional EC (HR 1.15; 95% CI 1.03–1.29; p = 0.01). In the multivariate analysis, several socioeconomic and tumor factors were found to be independently associated with survival by race, including county of residence income and prevalence of smoking, tumor grade, stage, and primary site, and surgical utilization. After adjusting for demographic and tumor characteristics, surgical utilization in patients with locoregional EC had a significant interaction with race on overall mortality (p = 0.01). Hispanics with locoregional EC were significantly less likely to receive surgery than whites (46 vs. 60%; p < 0.001) and not receiving surgery was associated with a significantly lower overall survival (HR 2.84; 95% CI 2.65–3.04; p < 0.001). Conclusions: A lower rate of surgery among Hispanics with potentially resectable esophageal cancer was associated with a decreased survival rate when compared to whites, even when adjusting for relevant socioeconomic and tumor factors. These data support the need to better address patient barriers to surgical treatment and the systemic biases present in medical care.

Prognostic stratification of locoregional esophageal cancer (EC) patients (pts) treated with definitive chemoradiotherapy (dCRT).

e15578 Background: Although dCRT is the standard treatment for pts who have locally advanced unresectable EC or refuse surgery, the prognosis of these pts remains dismal. There are urgent needs to develop the novel treatment strategy based on prognostic stratification after dCRT. Methods: A total of 382 pts with locoregional EC without distant metastasis except for supraclavicular lymph node who received dCRT at Asan Medical Center in South Korea from 2006 to 2015 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Risk factors were analyzed using Cox regression. Risk scores were calculated by multiplying coefficients in Cox proportional hazard model. Results: Baseline characteristics were as follows: median age = 66 yrs (range: 40-85); male = 359 pts (94.0%); squamous cell carcinoma = 375 (98.2%); cTNM stage (AJCC 8th) I = 40 (10.5%), II = 122 (31.9%), III = 128 (33.5%), IV = 92 (24.1%). During median follow-up of 52.9 mo, median PFS was 13.5 mo (95% CI, 10.9-16.1), and median OS was 26.7 mo (95% CI, 19.8-33.7). In the univariate analyses, sex (only for PFS), weight loss (≥ 5 kg) during dCRT, cT stage, cN stage, cTNM stage, clinical response after dCRT, reason for dCRT were significant prognostic factors for PFS and OS. In the multivariate analyses, clinical response after dCRT, cTNM stage, and weight loss were independent prognostic factors for PFS and OS (Table). Risk-scoring model using these factors stratified pts into four groups: for median PFS (p &lt; 0.0001), group 1 = 58.2 mo (95% CI, 43.5-73.0), group 2 = 17.0 mo (95% CI, 11.9-22.1), group 3 = 9.0 mo (95% CI, 7.0-11.1), and group 4 = 3.9 mo (95% CI, 3.7-4.2); for median OS (p &lt; 0.0001), group 1 = 106.2 mo (95% CI, 44.9-167.6), group 2 = 38.0 mo (95% CI, 24.4-51.5), group 3 = 13.0 mo (95% CI, 8.5-17.6), and group 4 = 8.0 mo (95% CI, 7.4-8.6). Conclusions: In dCRT-treated locoregional EC pts, survival outcome significantly varied according to baseline clinical stage, treatment response, and dynamic change in body weight. Different treatment and surveillance strategies based on the risk score might be needed in these pts.[Table: see text]

Neoadjuvant or Definitive Chemoradiation for Locoregional Esophageal Cancer and its Outcome at South Egypt Cancer Institute (Retrospective Study)

AbstractBackground: It is well known about esophageal carcinoma, the aggressive and invasive nature, in addition to the poor outcome. The experience of south Egypt cancer institute was to review the locally advanced esophageal carcinoma, treated by chemo radiation either followed by surgery or not, and their outcome.Aim of Study: In this study, we evaluate the efficacy of chemoradiation as a definitive or preoperative treatment.Patients and Methods: During the period June 2008, till June 2014, 55 patients with locally advanced esophageal cancer were reviewed for treatment with preoperative or definitive concurrent chemo radiation, at Radiation Oncology Department, South Egypt Cancer Institute, Assiut University. Statistical analysis of data was done by the statistical package for the social science (SPSS) version 20.Results: Out of 55 patients, 26 patients were included for definitive chemo radiation (dCRT). And 29 patients were included for neoadjuvant chemo radiation (nCRT). Squamous cell carcinoma (SqCC) represented in 72.7% of patients. Patients had disease stage II and III (32.7% and 67.3%) respectively. Median total radiation dose was 50.4 Gy over 28 fractions. Cisplatin+Fluorouracil regimen was received by 30 (54.5%) patients, while Paclitaxel+Carboplatin regimen was received by 25 (45.5%) patients. Overall response (CR+PR) was observed in 34 (72.3%) patients, while disease progression occurred in 5 (10.6%) patients and 17% (8 patients) had stable disease. The disease stage at diagnosis was a significant factor affecting clinical response. Out of 29 patients at neoadjuvant group, 18 patients (62%) underwent surgery, without major postoperative complications. Complete patho-logical response (no residual cancer cells) was observed in 6 (33%) patients. Median OS for dCRT and nCRT was 21 and 39 months respectively, it was in favor for nCRT group with no statistical significance (p-value=0.20). Median PFS for dCRT and nCRT was 16 and 18 months respectively, with no statistical significance (p-value=0.363). Disease stage at diagnosis and clinical response after radiotherapy were very highly significant factors affecting patients' overall survival and disease progression survival (p-value=0.014). Overall grade ³3 toxicity 26 events was observed in 16 (29.0%) of the patients.Conclusion: Neoadjuvant chemo radiation followed by surgery is considered as a standard care management for patients with resectable locally advanced esophageal carcinoma and fit for surgery. For patients with inoperable disease or unfit for surgery, definitive chemo radiation is accepted treatment option. The used chemotherapy regimens, Cispla-tin/Fluorouracil and Paclitaxel/Carboplatin, are tolerable in most patients with acceptable toxicity profile; and with no differences between two regimens.