Treatment Patterns and Outcomes in Patients with Esophageal Cancer: An Analysis of a Multidisciplinary Tumor Board Database.

BACKGROUND: Multidisciplinary management strategies are standard in esophageal cancer. Based on a multidisciplinary tumor board (MTB) database in a high-volume center, we aimed to evaluate real-world treatment patterns and patient outcomes in patients with esophageal cancer. In addition, we determined the impact of MTB discussions on patient prognosis. METHODS: Patients diagnosed with esophageal cancer between 2010 and 2019 were retrospectively reviewed. The pattern of treatment modalities and overall survival (OS) of patients with limited, locally advanced, and advanced/metastatic disease were reported. RESULTS: Data from 1132 patients, including 247 patients with limited esophageal cancer, 606 patients with locally advanced esophageal cancer, and 279 patients with advanced/metastatic esophageal cancer were included. Upfront surgery was the most common (56.3%) treatment modality for patients with limited esophageal cancer, while treatment for locally advanced esophageal cancer included upfront surgery (19.1%), neoadjuvant chemoradiotherapy (44.9%), and definitive chemoradiotherapy (36.0%); however, 27.9% of patients undergoing neoadjuvant chemoradiotherapy did not receive planned esophagectomy. Definitive chemoradiotherapy was mainly used for patients with locally advanced and advanced/metastatic disease, but had an incompletion rate of 22.0% and 33.7%, respectively. Regarding survival, the 5-year OS rates were 56.4%, 26.3%, and 5.1% in patients with limited, locally advanced, and advanced/metastatic disease, respectively. Additionally, patients whose clinical management was discussed in the MTB had a significantly better 5-year OS rate than the other patients (27.3% vs. 20.5%, p < 0.001). CONCLUSIONS: We report the real-world data of treatment patterns and patient outcomes in patients with esophageal cancer with respect to multidisciplinary management, and demonstrate the positive impact of MTB discussions on patient prognosis.

Predictors of adherence, contamination and dropout in home-based walking by lung and oesophageal cancer patients from two randomised control trials: An exploratory study.

OBJECTIVES: In this study, we examined predictors of exercise adherence, contamination and dropout in lung and oesophageal cancer patients who participated in two randomised controlled trials. METHODS: We used data on 188 lung and oesophageal cancer patients from two previous studies (intervention: moderate-intensity walking for 12 weeks). Baseline measurements included demographic variables, disease characteristics, Hospital Anxiety and Depression Scale and Bouchard 3-day physical activity (PA) record. We used multiple linear and logistic regressions to analyse predictors of exercise adherence in the walking group, contamination in the control group and dropout in both groups. RESULTS: Pre-intervention exercise habits and baseline depression scores predicted adherence, with an explanatory power of 16.7% (p < 0.0001). Pre-intervention exercise habits (odds ratio [OR] 19.65, 95% confidence interval [CI] 2.76-139.97), baseline moderate PA (min/day) (OR 1.03, 95% CI 1.01-1.05) and baseline vigorous PA (min/day) (OR 1.09, 95% CI 1.01-1.18) predicted contamination. Baseline mild PA (10 min/day) (OR 0.94, 95% CI 0.89-0.99) predicted dropout. CONCLUSIONS: Pre-intervention exercise habits and baseline depression levels predicted exercise adherence in the walking group. In the control group, pre-intervention exercise habits and baseline moderate and vigorous PA predicted contamination. Baseline mild PA predicted dropout rates in both groups.

Clinicopathological Significance of Pathologic Complete Lymph Node Regression After Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Pathologic complete lymph node regression (LNR), where the lymph nodes show evidence of neoadjuvant treatment effect but have no viable residual tumor cells, is sometimes observed following neoadjuvant treatments and has been shown to be prognostic; conflicting results exist in the current literature. METHODS: Patients who received neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for squamous carcinoma (ESCC) were retrospectively reviewed and classified according to their LNR score; 0: N(-) with no evidence of tumor involvement or regression; 1: N(-) with evidence of complete regression; 2: N(+) with < 50% viable tumor; and 3: N(+) with > 50% viable tumor. RESULTS: In total, 136 patients, comprising 73, 25, 16, and 22 patients with LNR scores of 0, 1, 2, or 3, respectively, were included. Pathologic complete LNR (LNR 1) was significantly associated with lower risks of lymphovascular invasion (0%, p < 0.001) and perineural invasion (4%, p = 0.038), and a higher rate of pathologic complete response in the primary tumor (76%, p < 0.001). The 5-year overall survival rates were 42.1%, 52.8%, and 8.0% in patients with an LNR score of 0, 1, and 2/3, respectively (p < 0.001). There was no significant difference between patients with LNR scores of 0 and 1 in overall survival (p = 0.454), disease-free survival (p = 0.501), and cumulative incidence of recurrences (hazard ratio 0.84, 95% confidence interval 0.432-1.623, p = 0.601). CONCLUSIONS: Pathologic complete LNR could be an indicator of nCRT sensitivity and can be regarded as a good prognostic factor in patients with ESCC. In the survival curve analysis that included patients with lymph node regression (LNR) scores of 0 (blue), 1 (red), and 2/3 (green), we found that patients with pathologic complete LNR (LNR 1), which suggests prior positive nodal involvement, had similar outcomes as those without evidence of prior tumor involvement in lymph node (LNR0).

The Prognostic Impact of Extracapsular Lymph Node Involvement in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The role of extracapsular lymph node involvement (ELNI) in esophageal cancer has not been fully investigated. We aim to assess its incidence and prognostic significance in patients with esophageal squamous cell carcinoma (ESCC) treated with and without neoadjuvant treatments. METHODS: Data of patients who underwent esophagectomy for ESCC in a single medical center was retrospectively reviewed. Patients with positive lymph node involvement were classified as either with ELNI or without ELNI (intracapsular lymph node involvement, ILNI). The impact of ELNI on overall survival (OS), disease-free survival (DFS), and disease recurrence was analyzed. RESULTS: A total of 336 patients, including 179 without (NCRT -) and 157 with (NCRT +) neoadjuvant chemoradiotherapy, were included. Seventy-two of 179 (40.2%) patients in NCRT - group were with positive lymph node, of whom 19 (26.4%) had ELNI, whereas 49 (31.2%) patients in NCRT + group had positive lymph node, of whom 25 (51.0%) had ELNI. In NCRT + group, patients with ELNI had worse outcome compared to those with ILNI in 5-year OS (10.4 vs. 13.8%, p = 0.008), and DFS (5.3 vs. 17.5%, p = 0.008). The presence of ELNI was also associated with more distant recurrence (p = 0.03). In contrast, there was no survival difference between patients with ELNI and ILNI in NCRT - group. CONCLUSIONS: Compared with ILNI, ELNI is a significant poor prognostic factor in patients with ESCC treated with neoadjuvant treatments, but not in those with primary surgery.

Prognostic histological factors in patients with esophageal squamous cell carcinoma after preoperative chemoradiation followed by surgery.

BACKGROUND: Pathological response is an important marker for tumor aggressiveness in patients with esophageal squamous cell carcinoma (ESCC) who receive preoperative chemoradiation followed by esophagectomy. We aim to evaluate the prognostic value of histological factors after trimodality treatments. METHODS: 91 patients who received preoperative chemoradiation followed by transthoracic esophagectomy between 2009 and 2014 were included. The pathological examination was reviewed. Overall survival and disease free survival were recorded. Survival analysis was performed using the Cox regression model, and the survival curves were compared by the log-rank test. RESULTS: Survival analysis showed lymphovascular invasion (LVI, hazard ratio [HR]: 2.009, p = 0.029), perineural invasion (PNI, HR: 2.226, p = 0.019), ypN stage (HR: 2.041, p = 0.019), extracapsular invasion (ECI, HR: 2.804, p = 0.003), and incomplete resection (HR: 1.897, p = 0.039) as unfavorable prognostic factors affecting overall survival (OS). Moreover, tumor regression grade (TRG, HR: 1.834, p = 0.038), LVI (HR: 1.975, p = 0.038), ECI (HR: 2.836, p = 0.003), and incomplete resection (HR: 2.254, p = 0.007) adversely affected disease-free survival (DFS). Prognostic classification based on poor primary tumor (TRG2/3, LVI(+), and PNI (+)), lymph node (ypN(+) and ECI(+)), and surgical (incomplete resection) factors significantly predicts OS (p = 0.013) and DFS (p = 0.017). However, the use of postoperative adjuvant therapy was not a significant prognostic factor even in medium- and high-risk ESCC patients who underwent trimodality treatments. CONCLUSIONS: Histological factors, including primary tumor, lymph node, and surgical factors has high prognostic value for predicting outcomes in ESCC patients receiving preoperative chemoradiation followed by surgery.

Moderating Effect of Daylight Exposure on the Relationship Between Physical Activity and Sleep in Patients with Upper Digestive Cancer: An Exploratory Study.

OBJECTIVES: To examine the moderating effect of daylight exposure on physical activity and objective sleep quality, using wearable actigraph devices. METHODS: We recruited 324 patients with either gastric or esophageal cancer. Actigraphs were used to measure all objective data including daylight exposure, physical activity, and sleep quality. Pearson's correlation coefficients were used to examine the relationships among demographic data, disease attributes, physical activity, daylight exposure, and sleep. The Hayes PROCESS macro with the regression bootstrapping method was employed to analyze the moderating effect of daylight exposure on the relationship between physical activity and sleep. RESULTS: Sleep efficiency correlated positively with physical activity, while "wake after sleep onset" correlated negatively with physical activity and mean lux. Mean lux and light >500 lux significantly moderated the association between physical activity and sleep efficiency (P = .002 in both cases). Similarly, mean lux and light >500 lux significantly moderated the association between physical activity and "wake after sleep onset" (P = .002 and .001, respectively). CONCLUSION: Both average daylight exposure and time of exposure to >500 lux act as moderators of physical activity and objective sleep quality in patients with gastric or esophageal cancer. Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality. IMPLICATIONS FOR NURSING PRACTICE: Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality.

Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer.

Among patients with unresectable or metastatic esophageal cancer who receive definitive chemotherapy or chemoradiotherapy, the rates of treatment-related adverse events and incomplete treatment remain high. We conducted this study to investigate survival after definitive treatments and identify predicting factors for incomplete treatment. The data of patients who received definitive chemotherapy or chemoradiotherapy for esophageal cancer were retrospectively examined. The patients were assigned to Group 1: incomplete definitive treatment; Group 2: complete definitive treatment; or Group 3: complete definitive treatment with additional salvage surgery. The data of 273 patients (90, 166, and 17 in Groups 1, 2, and 3, respectively) were analyzed. In the survival analysis, the median overall survival of Groups 1, 2, and 3 were 2.6, 10.3, and 29.5 months, respectively. A significant difference in 3-year overall survival was observed among the groups (2.2%, 12.4%, and 48.5%, p < 0.001). In multivariable analysis, the independent risk factors for incomplete definitive treatment included poor performance score (hazard ratio (HR): 5.23, p = 0.001), bone metastasis (HR: 2.18, p = 0.024), airway invasion (HR: 2.90, p = 0.001), and liver cirrhosis (HR: 3.20, p = 0.026). Incomplete definitive treatment is associated with a far worse prognosis. Poor performance, bone metastasis, airway invasion, and liver cirrhosis are risk factors for incomplete treatment.

Modified En Bloc Esophagectomy for Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND: The optimal type of esophagectomy and extent of lymphadenectomy for patients after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma remain controversial. We hypothesized that a more radical resection is associated with better survival. METHODS: Data of patients who received nCRT followed by resection for esophageal squamous cell carcinoma between 2012 and 2021 were analyzed. Modified en bloc esophagectomy (mEBE) involves total mediastinal lymphadenectomy and resection of all periesophageal node-bearing tissues. Perioperative outcomes and survival rates of mEBE were compared with those of conventional esophagectomy (CE). RESULTS: A total of 238 patients were included. Compared with CE, mEBE was associated with a longer operative time, higher total number of resected lymph nodes, fewer complications, and less anastomotic leakage; length of stay was similar between the 2 groups. There was no difference in overall survival rates between patients with ypT0 N0 stage in the mEBE and CE groups; however, in patients with non-ypT0 N0 stage in the mEBE and CE groups, the 3-year overall survival rates were 58.5% and 28.5%, respectively (P < .001). On disease-free survival analysis, no difference was observed in patients with ypT0 N0 stage, whereas patients with non-ypT0 N0 stage after nCRT had significantly better disease-free survival after mEBE compared with CE (49.7% vs 27.2%; P = .017). CONCLUSIONS: Survival after mEBE was significantly better than that after CE. The mEBE did not increase postoperative hospital stay and complication rates.

Clinical outcome of patients after recurrent laryngeal nerve lymph node dissection for oesophageal squamous cell carcinoma.

OBJECTIVES: Recurrent laryngeal nerve lymph node dissection (LND) has been incorporated into oesophagectomy for patients with oesophageal squamous cell carcinoma, but with uncertain oncological efficacy. METHODS: The data of patients with oesophageal squamous cell carcinoma, including who underwent upfront surgery (surgery group) and those who received neoadjuvant therapy followed by surgery (neoadjuvant chemoradiotherapy group), were retrospectively examined. The overall survival (OS) and disease-free survival (DFS) were compared between patients with and without recurrent laryngeal nerve LND. RESULTS: Among the 312 patients, no significant differences were found in 3-year OS and DFS between patients with and without recurrent laryngeal nerve LND in the entire cohort (OS: 57% vs 52%, P = 0.33; DFS: 47% vs 41%, P = 0.186), or the surgery group (n = 173, OS: 69% vs 58%, P = 0.43; DFS: 52% vs. 48%, P = 0.30) and the neoadjuvant chemoradiotherapy group (n = 139, OS: 44% vs 43%, P = 0.44; DFS: 39% vs 32%, P = 0.27). However, among patients with clinical positive recurrent laryngeal nerve lymph node involvement before treatment, there was significant OS and DFS differences between patients with and without recurrent laryngeal nerve LND (OS: 62% vs 33%, P = 0.029; DFS: 49% vs 26%, P = 0.031). CONCLUSIONS: Recurrent laryngeal nerve LND is not a significant prognostic factor in patients with oesophageal squamous cell carcinoma; however, it is associated with better outcomes in patients with pre-treatment radiological evidence of recurrent laryngeal nerve lymph node involvement.

Prognostic Effect of the Dose of Radiation Therapy and Extent of Lymphadenectomy in Patients Receiving Neoadjuvant Chemoradiotherapy for Esophageal Squamous Carcinoma.

Neoadjuvant chemoradiotherapy has been used for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal dose of radiation therapy and the effect of lymphadenectomy after neoadjuvant therapy on patient outcomes are uncertain. We retrospectively reviewed the data of patients who received neoadjuvant therapy followed by surgery for ESCC. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were compared between patients who received radiation doses of 45.0 Gy (PF4500) and 50.4 Gy (PF5040). Subgroup analysis was performed based on the number of lymph nodes removed through lymph node dissection (LND). Data from a total of 126 patients were analyzed. No significant differences were found in 3-year OS and DFS between the PF4500 and PF5040 groups (OS: 45% versus 54%, p = 0.218; DFS: 34% versus 37%, p = 0.506). In both groups, no significant differences were found in 3-year locoregional-specific DFS between patients with a total LND number ≤17 and >17 (PF4500, 35% versus 50%, p = 0.291; PF5040 group, 45% versus 46%, p = 0.866). The PF5040 and PF4500 groups were comparable in terms of survival outcomes and local control. Although no additional survival benefits were identified, the extent of LND should not be altered according to the radiation dose.

Effects of Rehabilitation Program on Quality of Life, Sleep, Rest-Activity Rhythms, Anxiety, and Depression of Patients With Esophageal Cancer: A Pilot Randomized Controlled Trial.

BACKGROUND: Esophageal cancer patients experience severe symptoms and poor quality of life. OBJECTIVE: We examined the effects of a rehabilitation program on quality of life, sleep, rest-activity rhythms, anxiety, and depression of esophageal cancer patients. METHODS: Forty-four patients with esophageal cancer were randomly assigned to an experimental group, which underwent a 12-week brisk walking and diet education program, or a control group, which received standard care. Health-related quality of life, subjective and objective sleep quality, rest-activity rhythms, anxiety, and depression were assessed at baseline and post intervention. RESULTS: A generalized estimating equation analysis revealed that, after intervention, compared with the control group, the experimental group exhibited significantly improved reflux (P = .022; effect size, 0.32) and marginally improved emotional (P = .069; effect size, 0.27) and social (P = .069; effect size, 0.27) functions; constipation (P = .050; effect size, 0.29), eating difficulty (P = .058; effect size, 0.27), anxiety (P = .050; effect size, 0.29), and total sleep time (P = .068; effect size, 0.39). CONCLUSIONS: The rehabilitation program may improve health-related quality of life and sleep and alleviate anxiety in patients with esophageal cancer. IMPLICATIONS FOR PRACTICE: A rehabilitation program comprising exercise and diet education is a feasible and low-cost intervention for improving quality of life of patients with esophageal cancer. Healthcare team members may consider it as a nonpharmacological treatment option for patients.

Predicting aggressive histopathological features in esophageal cancer with positron emission tomography using a deep convolutional neural network.

BACKGROUND: The presence of lymphovascular invasion (LVI) and perineural invasion (PNI) are of great prognostic importance in esophageal squamous cell carcinoma. Currently, positron emission tomography (PET) scans are the only means of functional assessment prior to treatment. We aimed to predict the presence of LVI and PNI in esophageal squamous cell carcinoma using PET imaging data by training a three-dimensional convolution neural network (3D-CNN). METHODS: Seven hundred and ninety-eight PET scans of patients with esophageal squamous cell carcinoma and 309 PET scans of patients with stage I lung cancer were collected. In the first part of this study, we built a 3D-CNN based on a residual network, ResNet, for a task to classify the scans into esophageal cancer or lung cancer. In the second stage, we collected the PET scans of 278 patients undergoing esophagectomy for a task to classify and predict the presence of LVI/PNI. RESULTS: In the first part, the model performance attained an area under the receiver operating characteristic curve (AUC) of 0.860. In the second part, we randomly split 80%, 10%, and 10% of our dataset into training set, validation set and testing set, respectively, for a task to classify the scans into the presence of LVI/PNI and evaluated the model performance on the testing set. Our 3D-CNN model attained an AUC of 0.668 in the testing set, which shows a better discriminative ability than random guessing. CONCLUSIONS: A 3D-CNN can be trained, using PET imaging datasets, to predict LNV/PNI in esophageal cancer with acceptable accuracy.

Lymphovascular Invasion as the Major Prognostic Factor in Node-Negative Esophageal Cancer After Primary Esophagectomy.

BACKGROUND: Studies addressing both lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with esophageal squamous cell carcinoma (ESCC) treated with or without neoadjuvant therapy are limited. We aimed to analyze the incidence and prognostic significance of LVI and PNI in patients with thoracic ESCC. METHODS: This retrospective study included 520 patients with ESCC: 174 patients after neoadjuvant treatment followed by surgery and 346 after primary esophagectomy, from two medical centers. The relationships between LVI, PNI, and other histological factors were evaluated. The Cox regression model was used for survival analysis. RESULTS: Positive LVI and PNI were noted in 35.6% and 22.4% of patients with residual primary tumor after neoadjuvant treatment and in 39.6% and 24.0% of patients who underwent primary esophagectomy, respectively. In patients with neoadjuvant treatments, the 5-year overall survival rates were 12.7% and 28.3% in patients with positive LVI and negative LVI, respectively (p = 0.001). The 5-year overall survival rates were 6.4% and 29.9% in patients with positive PNI and negative PNI, respectively (p < 0.001). In patients who did not receive neoadjuvant treatment, the 5-year overall survival rates were 28.2% and 61.1% in patients with positive LVI and negative LVI, respectively (p < 0.001). The 5-year overall survival rates were 30.2% and 52.5% in patients with positive PNI and negative PNI (p < 0.001). In subgroup analysis, the presence of PNI was an independent prognostic factor in patients with neoadjuvant treatments, whereas the presence of LVI had more significant prognostic impact in patients with node-negative ESCC after primary esophagectomy. CONCLUSIONS: Both LVI and PNI statuses are significant prognostic factors for patients with ESCC. However, the prognostic impact of LVI was majorly in the subgroup of node-negative patients who received primary esophagectomy.

Impact of perineural invasion as a histopathological prognostic factor in ypStage II/III oesophageal squamous cell carcinoma†.

OBJECTIVES: The 8th edition American Joint Committee on Cancer Tumour-Nodes-Metastasis (TNM) staging system distinguishes between the clinical (c), pathological (p) and post-neoadjuvant pathological (yp) stage groups. However, the ability to discriminate between ypStage II and ypStage III is poor. We aim to identify prognostic factors in patients with ypStage II/III oesophageal squamous cell carcinoma. METHODS: The data of 150 patients with ypStage II/III oesophageal squamous cell carcinoma from 2 medical centres were retrospectively reviewed. The neoadjuvant treatments included chemotherapy with cisplatin and 5-fluorouracil, administered concurrently with external beam radiation. The determination of perineural invasion (PNI) was based on pathological reports. Survival curves were compared using the log-rank test, and multivariable survival analysis was performed with a Cox regression model. RESULTS: The 3-year/5-year overall survival rate/median survival in ypStages II, IIIa and IIIb were 35.3%/26.9%/21.9 [95% confidence interval (CI) 14.9-28.8] months, 33.8%/22.5%/22.4 (95% CI 20.1-24.7) months and 21.7%/14.0%/14.4 (95% CI 11.1-17.7) months, respectively (P = 0.07). The 3-year/5-year overall survival rate/median survival was 36.7%/26.4%/22.8 (95% CI 19.2-26.5) months in the absence of PNI and 6.9%/3.4%/9.1 (95% CI 8.9-9.4) months in the presence of PNI (P < 0.001). In the multivariable survival analysis, tumour location in the upper third of the thoracic oesophagus [hazard ratio (HR) 1.692, 95% CI 1.087-2.635; P = 0.020] and positive PNI (HR 3.316, 95% CI 2.005-4.905; P < 0.001) remained as independent prognostic factors. CONCLUSIONS: The existence of PNI after neoadjuvant treatment is closely associated with poor prognosis and could be incorporated into the TNM staging system for better discrimination between patients with ypStage II/III oesophageal squamous cell carcinoma.

Deep Convolutional Neural Network-Based Positron Emission Tomography Analysis Predicts Esophageal Cancer Outcome.

In esophageal cancer, few prediction tools can be confidently used in current clinical practice. We developed a deep convolutional neural network (CNN) with 798 positron emission tomography (PET) scans of esophageal squamous cell carcinoma and 309 PET scans of stage I lung cancer. In the first stage, we pretrained a 3D-CNN with all PET scans for a task to classify the scans into esophageal cancer or lung cancer. Overall, 548 of 798 PET scans of esophageal cancer patients were included in the second stage with an aim to classify patients who expired within or survived more than one year after diagnosis. The area under the receiver operating characteristic curve (AUC) was used to evaluate model performance. In the pretrain model, the deep CNN attained an AUC of 0.738 in identifying patients who expired within one year after diagnosis. In the survival analysis, patients who were predicted to be expired but were alive at one year after diagnosis had a 5-year survival rate of 32.6%, which was significantly worse than the 5-year survival rate of the patients who were predicted to survive and were alive at one year after diagnosis (50.5%, p < 0.001). These results suggest that the prediction model could identify tumors with more aggressive behavior. In the multivariable analysis, the prediction result remained an independent prognostic factor (hazard ratio: 2.830; 95% confidence interval: 2.252-3.555, p < 0.001). We conclude that a 3D-CNN can be trained with PET image datasets to predict esophageal cancer outcome with acceptable accuracy.

Lymphovascular invasion and extracapsular invasion are risk factors for distant recurrence after preoperative chemoradiotherapy and oesophagectomy in patients with oesophageal squamous cell carcinoma.

OBJECTIVES: Patients with oesophageal squamous cell carcinoma have a high risk of disease recurrence even after trimodality treatments, which include preoperative chemoradiotherapy and oesophagectomy. We aimed to identify the histological factors that are associated with loco-regional and distant recurrence. METHODS: A retrospective review of a prospectively established database identified patients who received preoperative chemoradiotherapy and oesophagectomy for squamous cell carcinoma. The impact of histological factors, including surgical resection margins, lymphovascular invasion (LVI), perineural invasion (PNI), extracapsular invasion (ECI) and tumour regression grade (TRG), on disease recurrence was analysed. RESULTS: A total of 116 patients treated between 2009 and 2015 were included. Sixty-one patients developed disease recurrence, including 25 loco-regional and 49 distant recurrences, with a median disease-free interval of 6 months. Positive histological surgical resection margins were significantly associated with loco-regional recurrence, whereas pre-treatment N stage, ypT stage, ypN stage, positive surgical resection margins, TRG, LVI, PNI, ECI and TRG were significant prognostic factors for distant recurrence. Upon multivariate analysis, cN stage [hazard ratio (HR): 4.049; 95% confidence interval (CI): 1.242-13.200, P = 0.020], LVI (HR: 3.658; 95% CI: 1.891-7.078, P < 0.001) and ECI (HR: 2.393; 95% CI: 1.202-4.763, P = 0.013) remained independent factors for distant recurrence. The 1- and 3-year freedom from distant recurrence rates were 71.8 and 65.6%, respectively, when both LVI and ECI factors were absent, compared to 17.6 and 14.1% when either or both were present ( P < 0.001). CONCLUSIONS: Patients with lymphovascular invasion and extracapsular invasion are at a high risk of distant recurrence after preoperative chemoradiotherapy and oesophagectomy. Effective systemic therapy and intensive surveillance are necessary in this group of patients.

Comparison of survival among neoadjuvant chemoradiation responders, non-responders and patients receiving primary resection for locally advanced oesophageal squamous cell carcinoma: does neoadjuvant chemoradiation benefit all?

OBJECTIVES: While neoadjuvant chemoradiation followed by surgery has been shown to improve the survival of patients with locally advanced oesophageal cancer, it is not known whether neoadjuvant chemoradiation has a beneficial or harmful effect on the non-responders. We aimed to compare the outcomes among neoadjuvant chemoradiation responders, non-responders and patients receiving primary oesophagectomies for resectable locally advanced oesophageal squamous cell carcinoma. METHODS: Eighty-four non-T1-2N0 oesophageal squamous cell carcinoma patients were included. Thirty-eight patients received primary resection and 46 patients received neoadjuvant chemoradiation. The overall survival of chemoradiation responders (<50% residual tumour), non-responders (>50% residual tumour and those who shifted to definitive chemoradiation instead of surgery due to tumour progression) and patients receiving primary resection were compared. Clinical parameters were also compared between responders and non-responders. RESULTS: There was no overall difference in survival between neoadjuvant chemoradiation and primary resection groups (2-year overall survival rates: 45.6 vs 54.3%, P = 0.442). In patients receiving neoadjuvant chemoradiation followed by surgery, pathological responders had significantly higher 2-year overall survival rates than non-responders (64.5 vs 38.9%, P = 0.043). While the pathological responders had the highest survival rate, clinicopathological non-responders (pathological non-responders and patients with tumour progression during the neoadjuvant chemoradiation period) demonstrated significantly worse outcomes than those receiving primary resection (32.0 vs 54.3%, P = 0.036). However, none of the clinical parameters, including blood profiles, images and baseline tumour characteristics, predicted the response to chemoradiation before treatment. CONCLUSIONS: Neoadjuvant chemoradiation non-responders demonstrated no benefit and an even worse outcome compared with those receiving primary resection for locally advanced oesophageal squamous cell carcinoma. However, no significant clinical parameters could be implemented in the clinics to predict the response to neoadjuvant chemoradiation before treatment.