Localized Esophageal Squamous Cell Carcinoma Research Articles

Surgical quality determines the long-term survival superiority of right over left thoracic esophagectomy for localized esophageal squamous cell carcinoma patients: a real-world multicenter study.

The objective was to compare the long-term overall survival (OS) of right versus left thoracic esophagectomy, and to evaluate whether surgical quality impacts comparison result. Controversy regarding the optimal thoracic esophagectomy approach persists for esophageal squamous cell carcinoma (ESCC). No study has assessed the effect of surgical quality in comparison between right and left approaches. The authors consecutively recruited 5556 operable ESCC patients from two high-volume centers in China, of whom 2220 and 3336 received right and left thoracic esophagectomy, respectively. Cumulative sum was used to evaluate the learning curve for operation time of right approach, as the indicator of surgical proficiency. With a median follow-up of 83.1 months, right approach, harvesting more lymph nodes, tended to have a better OS than left approach (Mean: 23.8 vs. 16.7 nodes; adjusted hazard ratio (HR)=0.93, 95% CI: 0.85-1.02). Subset analysis by the extent of lymphadenectomy demonstrated that right approach with adequate lymphadenectomy (≥15 nodes) resulted in statistically significant OS benefit compared with left approach (adjusted HR=0.86, 95% CI: 0.77-0.95), but not with limited lymphadenectomy. Subset analysis by surgical proficiency showed that proficient right approach conferred a better OS than left approach (adjusted HR=0.75, 95% CI: 0.64-0.88), but improficient right approach did not have such survival advantage. Surgical quality plays a crucial role in survival comparison between surgical procedures. Right thoracic esophagectomy performed with adequate lymphadenectomy and surgical proficiency, conferring more favorable survival than left approach, should be recommended as the preferred surgical procedure for localized ESCC.

Sintilimab Injection Combination with Concurrent Chemoradiotherapy (cCRT) in Patients with Localized Esophageal Squamous Cell Carcinoma: A Prospective, Multi-Center, Single-Arm Trial in Progress

Esophageal cancer had accounted for the sixth highest incidence and the fourth highest death rate in China. The predominant histological subtype is esophageal squamous cell carcinoma (ESCC). At initial diagnosis, more than half of patients with ESCC are unfit for surgery. An accepted alternative to surgery is concurrent chemoradiotherapy (cCRT); however, many patients experience local recurrence or distant metastasis after cCRT. Therefore, innovative therapies are needed. Sintilimab is a fully human IgG4 monoclonal antibody, exhibiting the highest affinity for human PD-1 and a lower off-rate, the PD-1 receptor occupancy of sintilimab on circulating T cells is superior. In previous studies, sintilimab, alone and in combination with chemotherapy, was generally well tolerated and had antitumor activity in patients with advanced ESCC. This prospective, single-arm study (NCT04602013) is designed to explore the efficacy of Sintilimab in combination with cCRT. Eligible patients have histologically confirmed localized ESCC for whom cCRT is suitable and surgery is unsuitable/ declined; patients couldn't have received prior chemoradiotherapy. Approximately 53 Chinese patients from 5 centers will be to receive sintilimab (body weight <60kg: 3mg/kg IV Q3W; body weight ≥60kg: 200mg IV Q3W) in combination with cisplatin (25 mg/m2 IV on Days 1-3 of each 3-week cycle) plus paclitaxel for injection (albumin bound) (180 mg/m2). and radiotherapy at a total dose of 60Gy. Duration of treatment will be up to 12 months for sintilimab, including two cycles for concurrent administration of chemotherapy and radiotherapy. Progression-free survival (PFS), assessed by a Blinded Independent Review Committee per RECIST v1.1, is the primary endpoint of the study. Secondary efficacy endpoints include overall response rate, duration of response, and overall survival. Incidence and severity of adverse events (CTCAE V5.0) and patient-reported outcomes of health-related quality of life are additional secondary endpoints. A total of 17 patients have completed sintilimab injection combination with concurrent chemoradiotherapy,17/53 (32%). Objective response rate (ORR) 62.5% and a median progression free survival (mPFS) 17 months. 1-year overall survival (OS) 88.2%. The most common AEs included granulocytopenia (43.7%), thrombo -cytopenia (56.2%), radiation esophagitis (50%), nausea and vomiting (50%), and immune pneumonia (18.7%). Of these AEs greater than grade 3 granulocytopenia (25.0%), thrombocytopenia (35.0%), radiation esophagitis (12.5%), and nausea and vomiting (31.3%), and one patient developed grade 3 immune pneumonia (6.2%), which recovered with treatment. The treatment of sintilimab with CCRT is safe and effective for localized ESCC patients, even with high-dose radiotherapy (60Gy). This study may help to address the unmet need for new therapeutic options for patients with localized ESCC.

Age plays an important role in the decision of definitive concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma (ESCC): a propensity-score matched analysis of multicenter data (3JECROG R-02A).

BackgroundTo examine the survival benefit of definitive concurrent chemoradiotherapy (CCRT) compared to radiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) using a real-world patient population.MethodsThis retrospective study included 2,762 patients with ESCC across ten medical centers in China from 2001 to 2017. A total of 1,133 patients received radiotherapy alone and 815 patients were treated with CCRT. The patient survival rates were assessed by propensity-score matching (PSM) and subgroup analysis.ResultsThe baseline characteristics were significantly different between the two groups, with the CCRT group showing a higher proportion of males, younger patients, cervical/upper thoracic cancers, and worse T and N stages. There were no significant differences in the clinical characteristics between the two groups after PSM. Before PSM, the median overall survival (OS) rates were 31.2 and 24.1 months in the CCRT and RT alone groups, respectively, demonstrating the superior therapeutic effects (TEs) of the CCRT. However, the median OS rates were not significantly different between the two groups after PSM (32.6 and 39.4 months in the CCRT and radiotherapy alone groups, respectively). The subgroup analyses revealed that the median OS was significantly better in the CCRT group compared to the radiotherapy alone group (37.5 vs. 25.1 months, respectively) in patients less than 70 years of age [hazard ratio (HR) 0.782, 95% confidence interval (CI): 0.657 to 0.932]. In contrast, in patients 70 years of age and older, the 5-year survival rate was poorer in the CCRT group (34.8%) compared to the radiotherapy alone group (73.4%). Therefore, CCRT was an independent poor prognostic risk factor (HR 3.206, 95% CI: 2.168 to 4.740).ConclusionsCCRT may not be suitable for all patients with localized ESCC. Younger patients less than 70 years of age might benefit significantly from CCRT. However, in patients aged 70 years and older, the potential survival benefit of CCRT and the optimal combination treatment regimens require further investigation.

The duration of systemic inflammatory response syndrome is a reliable indicator of long-term survival after curative esophagectomy for esophageal squamous cell carcinoma

We focused on the Systemic Inflammatory Response Syndrome (SIRS) duration after surgery for esophageal squamous cell carcinoma (ESCC) as the prognostic marker. We enrolled a total of 222 patients with local ESCC, who underwent curative esophagectomy between 2005 and 2015. SIRS was diagnosed according to the criteria as a condition involving two or more of the following factors after surgery: (a) body temperature of > 38°C or < 36°C; (b) heart rate > 90 beats/min; (c) respiratory rate > 20 breaths/min (d) WBC count > 12,000 or < 4000 cells/mm3. We defined SIRS duration as the total sum of the days defined as SIRS conditions during 7days after surgery. The SIRS duration was analyzed by Cox hazards modeling to determine the independent prognostic factors for overall survival (OS) and Cancer-specific survival (CSS). The cutoff point of SIRS duration was determined to be set at 5.0days according to the receiver operating characteristic (ROC) curve, which was plotted using 5-year OS as the endpoint. Of the 222 patients, 165 (74.4%) and 57 (25.6%) were classified as having short (< 5.0) and long (≥ 5.0) SIRS, respectively. The long SIRS was significantly associated with postoperative pneumonia (Hazard Ratio (HR):9.07; P < 0.01), great amount of blood loss during surgery (HR: 2.20: P = 0.04), preoperative high CRP value (HR: 2.45: P = 0.04) and preoperative low albumin (HR: 2.79: P = 0.03) by logistic-regression multivariate analysis. Cox Hazard Multivariate analyses revealed that long SIRS was a worse prognostic factor for OS (HR: 2.36; 95% Confidence Interval (CI):1.34-4.20, P < 0.01) and CSS (HR: 2.07; 95% CI:1.06-4.06, P = 0.03), while postoperative pneumonia and postoperative high CRP value were not worse prognostic factors for OS and CSS. SIRS duration is a more reliable prognostic marker than the development of pneumonia and high postoperative CRP value after surgery for ESCC. The surgeons should aim to reduce the SIRS duration to improve the prognosis of ESCC patients.

Validation of the post-neoadjuvant staging system of the American joint committee on cancer, 8th edition, in patients treated with neoadjuvant chemoradiotherapy followed by curative esophagectomy for localized esophageal squamous cell carcinoma

ObjectiveThe American Joint Committee on Cancer 8th edition staging system presents separate classifications for pTNM and post-neoadjuvant ypTNM (ypTNM-8th) to enhance prognostic prediction after neoadjuvant therapy and surgery. We aimed to validate the ypTNM-8th staging system and to compare the prognostication performance of ypTNM-8th with that of pTNM-7th and pTNM-8th in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). MethodsWe reviewed 207 ESCC patients treated with nCRT between January 2007 and December 2014 and compared the Akaike information criterion (AIC) and Harrell's C-index to determine the prognostic performance of each TNM system. ResultsSurvival curve analysis of pTNM-7th and -8th showed a stepwise drop in survival from ypT0N0 to advanced stages, whereas the survival outcome of ypStage III showed a better prognosis than that of ypStage II according to ypTNM-8th. Lymphovascular invasion, perineural invasion, and tumor regression grade were significantly associated with overall survival on univariate analysis. Each TNM system showed significant p-values for trend (p < 0.0001 each), but after adjusting for prognostic factors, ypTNM-8th did not significantly predict survival (p = 0.15), whereas pTNM-7th remained significant (p < 0.001). pTNM-7th incorporating ypT0N0M0 and ypT0 (is)N + M0 as separate groups was superior in prognostication as its AIC was smaller and its C-index was higher than those of pTNM-8th and ypTNM-8th, respectively. ConclusionsBecause ypTNM-8th did not provide sufficient prognostication for patients with ESCC treated with nCRT followed by esophagectomy, more sophisticated prognostic classification should be developed for the ypTNM staging system in these patients.

A phase III trial in progress comparing tislelizumab plus concurrent chemoradiotherapy (cCRT) with placebo plus cCRT in patients with localized esophageal squamous cell carcinoma (ESCC).

TPS475 Background: In China, esophageal cancer (EC) ranks as the eigth most common cancer and the sixth most common cause of cancer related death. The predominant histological subtype of EC is ESCC. At first diagnosis, more than half of patients (pts) with ESCC are unfit for surgery. An alternative to surgery is cCRT; however, many pts experience local failure or distant metastasis after cCRT. As such, innovative therapies are needed. Tislelizumab, an investigational humanized monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. In previous studies, tislelizumab, as a monotherapy and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with ESCC. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT03957590) is designed to compare the efficacy of tislelizumab versus placebo in combination with cCRT. Patients with histologically confirmed localized ESCC for whom cCRT is suitable and surgery is unsuitable/declined are being enrolled. Approximately 316 Chinese pts will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with cisplatin (25 mg/m2 IV on Days 1-3 of each 3-week cycle) plus paclitaxel (135 mg/m2 IV Q3W) and radiotherapy at a total dose of 50.4 Gy. An Independent Data Monitoring Committee will be established to assess the safety/tolerability of tislelizumab plus cCRT in the first 20 enrolled pts; monitoring across the study will occur at regular intervals thereafter. Progression-free survival (PFS), assessed by a Blinded Independent Review Committee per RECIST v1.1, is the primary endpoint. Secondary efficacy endpoints include overall response rate, duration of response, and overall survival. Incidence and severity of adverse events (CTCAE V5.0) and HRQoL are additional secondary endpoints. Exploratory endpoints include PFS rate at Years 1 and 2, pharmacokinetic profile, and predictive biomarker analyses. Clinical trial information: NCT03957590.

Risk Factors of Severe Benign Cicatricial Stricture After Definitive Chemoradiation for Localized T3 Esophageal Carcinoma.

Severe benign cicatricial stricture (SBCS) is a major complication after definitive chemoradiation therapy (dCRT) for esophageal squamous cell carcinoma (ESCC). This study was conducted to investigate risk factors of SBCS in patients with localized ESCC. This study included 197 patients with clinical stage (cSt) II/III ESCC with T3 primary tumor, treated with dCRT between 2000 and 2011. SBCS was defined as the inability to pass a 9-mm diameter endoscope or the presence of symptoms requiring treatment. Complete response was obtained in 87 patients (44%). Multivariate analysis revealed that hypoalbuminemia (hazard ratio=5.65; 95% confidence interval=1.50-21.28; p=0.010) and the inability to pass an endoscope (hazard ratio=5.90; 95% confidence interval=1.52-22.85; p=0.010) were risk factors of SBCS. The inability to pass an endoscope and hypoalbuminemia were identified as risk factors of SBCS in patients with cSt II/III ESCC with T3 primary tumor.

762P - Prognostic value of metabolic response assessed by 18FDG-PET after induction chemotherapy and after chemoradiotherapy (CRT) in localized esophageal squamous cell carcinoma (ESCC) patients (pts) receiving definite CRT (dCRT)

BackgroundAlthough, previous studies reported that metabolic response (MR) assessed by post-CRT 18FDG-PET was associated with survival outcomes in ESCC treated with dCRT, there are few data on the prognostic value of each metabolic response category after induction chemotherapy prior to dCRT and after completion of dCRT. MethodsIn this retrospective study, we evaluated prognostic value of MR after completion of induction chemotherapy and after completion of dCRT in 382 localized ESCC pts receiving induction chemotherapy followed by dCRT from January 2012 to February 2018 at Asan Medical Center in Korea. MR was assessed by EORTC criteria. ResultsMR after induction chemotherapy was significantly associated with progression-free survival (PFS) and overall survival (OS). MR after dCRT was also significantly associated with PFS and OS. MR after either induction chemotherapy or dCRT remained significant after adjusting for other prognostic factors such as clinical TNM stage, sex, and ECOG performance status. Whereas pts achieving mCR/mPR or mPD after either induction chemotherapy or dCRT had good prognosis or poor prognosis, respectively, the prognostic value of mSD was different between post-induction chemotherapy and post-dCRT; it was similar to that of mPR after induction chemotherapy, but it was similar to that of mPD after dCRT. Poorer MR to induction chemotherapy could predict the lack of MR after dCRT; the proportion of mSD/mPD after dCRT was 7.7% in pts with post-induction mCR vs. 16.0% in pts with vs. 40.0% in pts with post-induction mSD vs. 100% in pts with post-induction mPD (p=0.001).Table762PTablePost induction chemotherapyPost-dCRTmetabolic responseNHR for PFS (95% CI)P-valueHR for OS (95% CI)P-valueNHR for PFS (95% CI)P-valueHR for OS (95% CI)P-valuemCR131115011mPR1063.348 (1.221-9.181)0.0192.498 (1.008 - 6.192)0.0481642.182 (1.646-2.892)0.0002.224 (1.694-2.919)0.000mSD106.008 (1.179-20.150)0.0043.640 (1.186-11.171)0.024711.251 (5.088-24.878)0.0009.659 (4.393-21.236)0.000mPD259.209 (9.430-371.767)0.00014.495 (2.676-78.503)0.0023921.768 (14.020-33.797)0.00010.592 (7.016-15.989)0.000diffuse esophagitis31.729 (0.193-15.482)0.6241.103 (0.129-9.453)0.929221.169 (0.651-2.098)0.6011.482 (0.856-2.566)0.160Total1340.0000.0273820.0000.000 ConclusionsMR after induction chemotherapy and after CRT had independent prognostic value with different prognostication between each other in ESCC pts receiving induction chemotherapy followed by dCRT. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Thoracic Duct Resection During Esophagectomy Does Not Contribute to Improved Prognosis in Esophageal Squamous Cell Carcinoma: A Propensity Score Matched-Cohort Study.

Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal squamous cell carcinoma (ESCC). Thoracic duct (TD) resection has been recommended as part of extended lymphadenectomy, although its merits are unclear. The aim of this two-institutional, matched-cohort study is to clarify whether TD resection improves prognosis in esophagectomy for ESCC. In this two-institutional, matched-cohort study of 399 patients with ESCC who underwent McKeown esophagectomy between 2010 and 2014, the primary outcomes were overall survival (OS), disease-free survival (DFS), and cause-specific survival (CSS). Secondary outcomes were perioperative results and recurrence patterns. Based on a propensity score, 122 TD-resected or 122 TD-preserved patients in all stages were selected (median follow-up 4.5years). The 5-year OS, DFS, and CSS rates in the TD-resected versus TD-preserved groups were 49% versus 60%, 53% versus 57%, and 58% versus 70%, respectively, without any significant differences. Operative time for the thoracic procedure was significantly longer and the number of retrieved mediastinal nodes was significantly higher in the TD-resected group (P = 0.009 and 0.005, respectively). The rates of chylothorax and left recurrent laryngeal nerve (RLN) palsy were significantly higher in the TD-resected group (P = 0.041 and 0.018, respectively). There were no significant differences in rates of local or distant metastases between the two groups. TD resection does not contribute to improve OS, DFS, or CSS in ESCC but increases incidence of chylothorax and left RLN palsy. Prophylactic TD resection should be avoided in esophagectomy for ESCC.

Outcomes of Localized Esophageal Squamous Cell Carcinoma Patients Treated With Definitive Concurrent Chemoradiotherapy Using Either Standard or High Radiotherapy Dose: A Retrospective Study Controlling for Organ at Risk Dose.

The optimal radiotherapy dose for localized esophageal squamous cell carcinoma (ESqCC) patients treated with definitive concurrent chemo-radiotherapy (CCRT) is debated. The aim of our study was to compare patient outcomes using either standard or high radiotherapy dose. Eligible patients diagnosed between 2011 and 2015 from the cancer registry of our Institute were identified and a propensity score (PS)-matched cohort (1:1 for high vs. standard dose) was constructed to balance observable potential confounders (including organ at risk dose). The hazard ratio (HR) of death between high and standard dose was compared. Our study population included 73/36 patients before/after PS matching. The HR of death at the high dose compared to the standard dose was 0.554 (95% confidence interval (CI)=0.308-0.998, p=0.049). Definitive CCRT using a high radiotherapy dose showed improved survival outcomes for localized ESqCC patients compared to standard dose.

Effect of consolidation chemotherapy following definitive chemoradiotherapy in patients with esophageal squamous cell cancer

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48–1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44–0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

Definitive Intensity-Modulated Radiation Therapy With a Simultaneous Integrated Boost May Lead to Better Outcome for Non-operated Localized Esophageal Squamous Cell Carcinoma—Analysis from a Multicenter Study

The role of definitive intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) in treating non-operated localized esophageal squamous cell carcinoma (LESCC) remains unclear. We investigated the effect of SIB-IMRT on the survival outcome of patients with LESCC who receiving definitive radio/chemoradiotherapy. A total of 1606 patients with LESCC from nine institutions were retrospectively reviewed. Among them, 556 patients (34.6%) received SIB-IMRT which consisted a prognostic dose delivered to the planning target volume (PTV) with a median of 54 Gy/1.8-2.0Gy fraction. The boost dose was given to the primary tumor and metastatic regional lymph nodes to a median total dose of 61.5Gy/2.0-2.3Gy fraction. For patients with conventional fractionated radiotherapy (CFR), PTV was prescribed to 60Gy/1.8-2.0Gy fraction. A propensity score matching (PSM) method (1:1 for SIB-IMRT vs CFR) was used to identify 932 well-balanced patients for validation studies. Actuarial survival was calculated with the Kaplan-Meier method, and univariate comparison between groups was performed by using the log-rank test. Cox regression served as a multivariate technique using a backward elimination model for all covariates. Median age was 64 years, and most patients were male (72.7 %). Primary tumor location in cervical, upper, middle and lower of esophagus were determined in 6%, 35%, 48% and 12%. The patients were clinically staged as stage IIa/b (22%), III (56%), and IVa/b (without visceral metastasis or positive lymph node out of regional site) (22%), according to AJCC 6th TNM classification. After PSM, the 2-year overall survival (OS) and median survival were 51.5% and 28 months in SIB-IMRT group, which is significantly higher than that in CFR group (46.5% and 24 months, P<0.001). In the multivariate survival analysis, clinical stage (Hazard Ratio [HR]: 1.53, 95% CI: 1.38-1.97, P < 0.001), tumor length (HR: 1.05, 95% CI: 1.02-1.08, P = 0.001), female (HR: 0.81, 95% CI: 0.69-0.95, P = 0.011), concurrent chemoradiotherapy (HR: 0.76, 95% CI: 0.67-0.88, P < 0.001) and SIB-IMRT (HR: 0.89, 95% CI: 0.77-0.97, P = 0.034) were independent prognostic factors. Subgroup analysis suggested patients with age ≤70, upper 1/3 esophageal cancer, tumor length ≤5cm, and cN0 stage tumors were more likely to demonstrate survival benefit from SIB-IMRT. Compared with CFR, SIB-IMRT may provide a survival benefit to LESCC patients. A prospective study is needed to verify our findings and to provide scientific evidence for this subject.

The management of localized esophageal squamous cell carcinoma: Western approach.

Esophageal cancer remains a significant cause of cancer-related mortality worldwide and carries a poor prognosis both in the locally advanced and metastatic setting. Esophageal squamous cell carcinoma (ESCC) accounts for the majority of esophageal cancers globally, while esophageal adenocarcinoma (EAC) now predominates in the Western world. Historically, clinical trials have not separated the two histologic subtypes, with similar regimens being used for both. This, however, is changing with the recent publication by the Cancer Genome Atlas Research Group confirming that comprehensive analysis reveals ESCC demonstrates frequent genomic amplifications of CCND1 and SOX2 and/or TP63 and biologically are more like head and neck squamous cell carcinomas, whereas EACs strongly resemble the chromosomally unstable variant of gastric cancer. With a lack of viable targets in squamous cell carcinoma, immunotherapeutic approaches are now being investigated in both early stage and metastatic ESCC with promising results being reported in the preliminary data published to date.

631P - Prognostic stratification of pathologic stage in patients with preoperative chemoradiotherapy followed by curative esophagectomy for localized esophageal squamous cell carcinoma

631P - Prognostic stratification of pathologic stage in patients with preoperative chemoradiotherapy followed by curative esophagectomy for localized esophageal squamous cell carcinoma

Does higher radiation dose lead to better outcome for non-operated localized esophageal squamous cell carcinoma patients who received concurrent chemoradiotherapy? A population based propensity-score matched analysis

BackgroundThe optimal radiotherapy dose for non-operated localized esophageal squamous cell carcinoma (NOL-ESCC) patients undergoing concurrent chemoradiotherapy (CCRT) is hotly debated. MethodsWe identified eligible patients diagnosed within 2008–2013 from Taiwan Cancer Registry and constructed a propensity score matched cohort (1:1 for high dose (⩾60Gy) vs standard dose (50–50.4Gy)) to balance observable potential confounders. We compared the hazard ratio (HR) of death between standard and high radiotherapy dose groups during the entire follow-up period. We performed sensitivity analysis (SA) to evaluate the robustness of our finding regarding potential unobserved confounders & index date definition. ResultsOur study population constituted 648 patients with well balance in observed co-variables. The HR of death when high dose was compared to standard dose was 0.75 (95% confidence interval 0.64–0.88). Our result was sensitive to potential unobserved confounders but robust to alternative index date definition in SA. ConclusionsWe found that higher than standard radiotherapy dose may lead to better survival for NOL-ESCC patients undergoing CCRT.

Radical Lymph Node Dissection in Primary Esophagectomy for Esophageal Squamous Cell Carcinoma

Subtotal esophagectomy with radical lymph node dissection (RLND) remains an effective therapeutic strategy for localized esophageal squamous cell carcinoma (ESCC). However, controversy exists regarding the extent to which RLND should be performed. We reappraised the prognostic impact and accurate nodal staging of RLND in ESCC. The data from 101 ESCC patients (mean age, 57.5 years; 93 men) who underwent primary subtotal esophagectomy were retrospectively collected. Candidate variables, including the number of total dissected lymph nodes (TDLN [subgrouped into TDLN less than 13, TDLN 13 to 40, and TDLN more than 40]), were evaluated to determine their prognostic impacts and hazard ratio (HR). Fewer TDLN (p < 0.001; HR 9.011, 2.449, and 1.000 for TDLN less than 13, TDLN 13 to 40, and TDLN more than 40, respectively), tumor length exceeding 3.5 cm (p < 0.001; HR 3.321), resection margin invasion (p < 0.001; HR 14.493), and positive nodal status (p = 0.002; HR 2.730) were independent predictors of a poor prognosis. Considering the 54 node-negative patients, more TDLN correlated with improved survival (p = 0.001). Risk analysis demonstrated that one fewer TDLN could contribute to an increased HR of 1.047 (p = 0.014). However, RLND involving more TDLN appeared to lose the prognostic impact for the 47 node-positive patients (p = 0.072). Furthermore, the number of positive dissected lymph nodes remained at approximately 4 if the number of TDLN exceeded 20. For N-negative or N-positive ESCC patients undergoing primary surgical resection, the number of TDLN influenced their prognosis or nodal staging accuracy, respectively. At least 20 TDLN were necessary for N-positive patients.

STMN-1 Gene: A Predictor of Survival in Stage IIA Esophageal Squamous Cell Carcinoma After Ivor-Lewis Esophagectomy?

Prognosis of esophageal squamous cell carcinoma (ESCC) is stage-specific; however, some patients with the same stage have different survival outcomes. Clinically, it is significant to explore the biological marker to predict patient's outcome. We investigated the association between the stathmin1 gene (STMN-1) expression and the prognosis of patients who underwent Ivor-Lewis esophagectomy. A total of 162 patients who suffered from midthoracic stage IIA ESCC and completely resected with Ivor-Lewis esophagectomy were studied for STMN-1 expression by qRT-PCR in fresh-frozen tissue and validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples. STMN-1 level was evaluated as a prognostic factor in ESCC. SPSS 21.0 software was used to analyze the relationship between STMN-1 expression and clinicopathological characteristics and survival probability. The overall 3- and 5-year survival was 72.20 and 42.00 % respectively. Ninety-four patients (58.02 %) experienced disease recurrence with a disease-free interval of 21.50 ± 1.20 months. qRT-PCR result showed that STMN-1 mRNA level in patients who were alive at the end of follow-up was lower compared with patients who died during the follow-up period (p < 0.05). Immunohistochemical results showed that 94 patients had STMN-1 protein overexpression (58.02 %), patient with STMN-1 overexpression had worse survival compared with patients who had low STMN-1 expression (p = 0.00). Cox regression analysis revealed that STMN-1 protein expression and T classification are independent prognostic factors. Even localized ESCC are potential to relapse with poor prognosis. This study demonstrates that STMN-1 level is an independent prognostic factor after Ivor-Lewis esophagectomy. In addition, assessment of STMN-1 level could improve stratification of stage IIA ESCC patients.

A Retrospective Evaluation of Radiotherapy for the Treatment of Local Esophageal Squamous Cell Carcinoma Recurrence After Initial Complete Surgical Resection

IntroductionOur purpose was to assess the efficacy of radiation therapy in the treatment of locoregional recurrence of esophageal squamous cell carcinoma recurrence after curative resection.MethodsPatients with local esophageal squamous cell...

Mutational spectra of p53 in geographically localized esophageal squamous cell carcinoma groups in China.

Esophageal carcinoma is a particularly interesting tumor because of the dramatic difference in its incidence and geographic distribution among populations of similar ethnic origin. Epidemiologic data have suggested that many environmental exposures may be associated with an increased risk of its formation. In this study, 92 samples of esophageal squamous cell carcinoma (ESCC) were collected from patients who resided in 2 geographic areas in China with different incidences of ESCC: Linxian and Zhejiang. Overexpression and mutations of the p53 tumor-suppressor gene were examined by using immunohistochemistry, single-strand conformation polymorphism analysis, and direct sequencing. The rates of point mutation and overexpression of p53 in the ESCC specimens studied were 30.4% (29 of 92 specimens) and 51.1% (47 of 92 specimens), respectively. The overexpression of p53 was associated with tumor metastasis and with 5-year case fatality. Significant differences were found in the rates of overexpression and mutations in patients with clinical T2 tumors between the specimens from Linxian, which is a high-incidence geographic area, and the specimens from Zhejiang, which is a low-incidence area. Furthermore, different mutational spectra were found in the tumor samples from these two geographic areas: In tumor samples from Linxian, the most common substitution mutation was a transversion in exon 5, whereas the most common mutations in tumor samples from Zhejiang were transitions in exon 7. The data suggest that the mutation and overexpression of p53 may play important roles in the development of ESCC. The changes in p53 may reflect environmental exposure to the different combinations of mutagenic factors and genetic instability demonstrated by the populations in Linxian and Zhejiang. The overexpression of p53 protein may have significance as a prognostic factor for patients with esophageal carcinoma.

Neoadjuvant chemotherapy in squamous cell carcinoma of the esophagus using low dose continuous infusion 5-fluorouracil and cisplatin: Results of a prospective study

Surgery is the treatment of choice for localized esophageal squamous cell carcinoma (ESCC). Despite curative surgical resection, the majority of patients develop local and systemic recurrence with poor 5-year survival. To study the role of low dose continuous infusion (CI) 5-fluorouracil (5-FU) and cisplatin as neoadjuvant chemotherapy in ESCC. A non-randomized prospective study conducted over a period of two years (1996-1998) in the Department of Surgery, All India Institute of Medical Sciences, India. Twenty-two patients with ESCC were included in the study. Chemotherapy consisted of a continuous 30-day infusion of 5-FU (350 mg/m2/day) and cisplatin (7.5 mg/m2/day), 5 days/week for 4 weeks. All patients had surgery following chemotherapy. A full course of chemotherapy was completed in 18 patients (82%). Chemotherapy was not completed due to non-compliance (n=2), thrombophlebitis (n=1), and vomiting (n=1). Grade-1 haematological and hepato-toxicity was observed in four patients. Thirteen patients developed thrombophlebitis. After chemotherapy, improvement in dysphagia was observed in 13 of 22 (59%) patients. Radiological partial response was observed in 8 patients (36.4%). 19 patients underwent surgical resection (86.4%) with zero mortality. Post-operative morbidity was observed in six patients (27%). Complete and partial pathological response was observed in two (11%) and one patient (5.5%) respectively. The overall median survival was 18 months and 4-year survival was 42%. Low dose CI 5-FU and cisplatin is well tolerated with minimal toxicity. Histopathological response rates and survival figures are comparable with the more toxic neoadjuvant chemotherapeutic regimens.