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Background: The objective of this study was to investigate the relationship between clinical characteristics, as well as dosimetric parameters, and the risk of treatment‐related lymphopenia in esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). Materials and Methods: Clinical characteristics and dosimetric parameters were collected from 436 patients with ESCC who received definitive CRT from 2010 through 2017. Absolute lymphocyte counts (ALCs) were obtained before, during, and 1 month after CRT. Grade 4 (G4) lymphopenia was defined as ALC <0.2 × 109/L during CRT. Logistic regression analysis was used to evaluate the effect of each factor on predicting G4 lymphopenia. The relationship between lymphopenia and overall survival (OS) was examined, and a nomogram was developed to predict OS. Results: G4 lymphopenia was observed in 103 patients (23.6%) during CRT. Multivariate analysis indicated that planning target volume (PTV), lung V10, heart V10, performance status, and pretreatment lymphopenia were significant risk factors for G4 lymphopenia. Patients with G4 lymphopenia had significantly worse survival than those without. Based on multivariate analysis, clinical TNM stage, radiotherapy modality, pretreatment ALC, and G4 lymphopenia were predictive of OS and were incorporated into the nomogram, yielding a concordance index of 0.71. Conclusions: G4 lymphopenia during definitive CRT was associated with larger PTVs, higher lung V10 and heart V10, and worse survival. Implications for Practice: The purpose of this study was to investigate the relationship between clinical characteristics, as well as dosimetric parameters, and the risk of treatment‐related lymphopenia in 436 patients with esophageal squamous cell carcinoma who received definitive chemoradiotherapy. Grade 4 (G4) lymphopenia was observed in 23.6% of patients during radiotherapy. G4 lymphopenia was associated with larger planning target volumes, higher lung V10 and heart V10, and worse survival. Then, a nomogram was built based on multivariate analysis, yielding excellent performance to predict overall survival. Prospective studies are needed to investigate potential approaches for mitigating severe lymphopenia, which may ultimately convert into survival benefits. This study explored the relationship between clinical characteristics, as well as dose‐volume histogram parameters, and the risk of treatment‐related lymphopenia in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. This article evaluates whether lymphopenia is associated with patient outcomes and describes a nomogram built to predict survival. [ABSTRACT FROM AUTHOR]

Background: To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery.Methods: Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT.Results: With a median follow-up of 34 months (range, 2-116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%).Conclusions: 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors. [ABSTRACT FROM AUTHOR]

Lessons Learned: Weekly treatment with 5‐fluorouracil and cisplatin, concurrent with radiotherapy, achieved promising response rates in patients with postoperative recurrent esophageal squamous cell carcinoma.Superior toxicity results were also found. Background: Concurrent chemoradiotherapy (CCRT) is one of the treatment strategies for patients with esophageal squamous cell carcinoma (ESCC) with postoperative locoregional recurrence. However, the once every 3 weeks chemotherapy regimen causes a high incidence of toxicity. The aim of this study was to evaluate the efficacy and toxicity of weekly 5‐fluorouracil (5‐FU) and cisplatin concurrent with radiotherapy in postoperative locoregional recurrent ESCC. Materials and Methods: Patients received four weekly chemotherapy cycles of cisplatin (25 mg/m2, day 1) plus 5‐FU (1,176 mg/m2, day 1–3), and concurrent with radiotherapy (50.4–60 Gy). The primary endpoint was objective response rate (ORR). Secondary objectives were toxicity, disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). Results: Between January 2013 and December 2015, 48 patients were enrolled. The ORR was 68.8% (12 patients with complete response, 21 patients with partial response), with DCR 68.8%. No treatment‐related grade 4 adverse events occurred. Grade 3 hematologic toxicities were observed in eight (17%) patients. Grade 3 vomiting or esophagitis occurred in four (8%) patients each. The median PFS and OS were 13.94 months (95% confidence interval [CI], 0.75–51.05) and 27.43 months (95% CI, 5.278–49.58; Fig. 1). Conclusion: Weekly 5‐FU and cisplatin concurrent with radiotherapy achieved a promising response rate and improved toxicity in patients with postoperative locoregional recurrent ESCC. [ABSTRACT FROM AUTHOR]

• Satisfactory survival outcomes for T4b ESCC patients with the median OS and 3- year OS rates of 12.2 months and 29.9% was observed in a cohort including 136 patients who were treated with CRT. • One third (30.1%) of the patients developed esophageal fistula and those patients that developed fistula had a significantly shorter OS. • Tumor ulceration and bronchus/trachea invasion are the two independent risk factors for developing esophageal fistula after CRT in T4b ESCC. Despite definitive chemoradiotherapy (CRT) being a recommended therapeutic method for patients with T4b esophageal squamous cell carcinoma (ESCC), treatment response and complications remain unclear. Esophageal fistula is a severe CRT-related complication when treating locally advanced ESCC, but data on risk factors that lead to esophageal fistula formation are limited. The aim of this analysis is to characterize the outcomes of T4b ESCC treated by CRT and investigate the risk factors of esophageal fistula. We retrospectively analyzed 136 patients with clinically unresectable T4b ESCC who were treated with CRT. Response, survival, and complication rates, particularly the rate of esophageal fistula and its associated risk factors were analyzed. The median progression-free survival and overall survival (OS) of all patients were 7.9 (95% confidence interval [CI]: 6.1–9.7) and 12.2 months (95% [CI]: 8.9–15.4), respectively. The Kaplan–Meier curves showed that the 3- and 5-year OS rates were 29.9% and 20.2%, respectively. The incidence rate of esophageal fistulas was 30.1%. The median OS for patients with esophageal fistula was only 6.9 (95%[CI] = 6.0–7.8) months. The risk for developing esophageal fistulas was significantly high for ulcerative-type tumors (odds ratio [OR] = 3.202; 95%[CI] = 1.036–7.850, P = 0.011) and for those invading the bronchus/trachea (OR = 3.378; 95%[CI] = 1.223–9.332, P = 0.048). We demonstrated that CRT for T4b ESCC patients has a curative potential, despite a high incidence of esophageal fistula, which was the main cause of treatment failure. The higher risk for fistula formation were tumors with ulceration or bronchus/trachea invasion. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare recurrence patterns and prognostic factors for developing recurrences in patients with oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (CRT) followed by surgery or surgery alone from a multicenter phase III trial NEOCRTEC5010. Patients with locally advanced ESCC were randomly assigned in a 1:1 ratio to receive neoadjuvant CRT plus surgery (CRT + S group) or surgery alone (S group). CRT consisted of two cycles of vinorelbine and cisplatin with concurrent radiotherapy of 40.0 Gy in 20 fractions. Recurrence patterns, sites, frequency, and timing and potential prognostic factors were compared. Of the 451 patients enrolled from 2007 to 2014, 411 patients who underwent resection were analysed. After a median follow-up of 51.9 months, 62 patients (33.7%) in the CRT + S group versus 104 patients (45.8%) in the S group experienced recurrences (P = 0.013). The CRT + S group demonstrated a significantly better locoregional failure-free survival (P = 0.012) and a more favourable distant metastasis-free survival (P = 0.028) than the S group. Recurrences occurred earlier in the S group (P = 0.053), and late relapses were much more frequent in the CRT + S group (P = 0.029). On multivariate analysis, R1 resection and surgery alone were adverse factors for developing locoregional recurrences, whereas R1 resection was the only independent factor associated with distant metastases. The neoadjuvant CRT regimen was associated with significantly reduced locoregional and distant recurrences compared with surgery alone. Recurrence patterns, sites and frequency were different between groups. NCT01216527. • neoadjuvant chemoradiotherapy regimen reduced locoregional and distant recurrences. • Recurrences occurred earlier in the surgery alone group. • Late relapses were much more frequent in the neoadjuvant chemoradiotherapy group. • R1 resection was an adverse factor for developing locoregional recurrences. • R1 resection was the only independent factor associated with distant metastases. [ABSTRACT FROM AUTHOR]