Resected Esophageal Cancer Patients Research Articles

Analyzing the Impact of Oncological Data at Different Time Points and Tumor Biomarkers on Artificial Intelligence Predictions for Five-Year Survival in Esophageal Cancer

AIM: In this study, we use Artificial Intelligence (AI), including Machine (ML) and Deep Learning (DL), to predict the long-term survival of resectable esophageal cancer (EC) patients in a high-volume surgical center. Our objective is to evaluate the predictive efficacy of AI methods for survival prognosis across different time points of oncological treatment. This involves comparing models trained with clinical data, integrating either Tumor, Node, Metastasis (TNM) classification or tumor biomarker analysis, for long-term survival predictions. METHODS: In this retrospective study, 1002 patients diagnosed with EC between 1996 and 2021 were analyzed. The original dataset comprised 55 pre- and postoperative patient characteristics and 55 immunohistochemically evaluated biomarkers following surgical intervention. To predict the five-year survival status, four AI methods (Random Forest RF, XG Boost XG, Artificial Neural Network ANN, TabNet TN) and Logistic Regression (LR) were employed. The models were trained using three predefined subsets of the training dataset as follows: (I) the baseline dataset (BL) consisting of pre-, intra-, and postoperative data, including the TNM but excluding tumor biomarkers, (II) clinical data accessible at the time of the initial diagnostic workup (primary staging dataset, PS), and (III) the PS dataset including tumor biomarkers from tissue microarrays (PS + biomarkers), excluding TNM status. We used permutation feature importance for feature selection to identify only important variables for AI-driven reduced datasets and subsequent model retraining. RESULTS: Model training on the BL dataset demonstrated similar predictive performances for all models (Accuracy, ACC: 0.73/0.74/0.76/0.75/0.73; AUC: 0.78/0.82/0.83/0.80/0.79 RF/XG/ANN/TN/LR, respectively). The predictive performance and generalizability declined when the models were trained with the PS dataset. Surprisingly, the inclusion of biomarkers in the PS dataset for model training led to improved predictions (PS dataset vs. PS dataset + biomarkers; ACC: 0.70 vs. 0.77/0.73 vs. 0.79/0.71 vs. 0.75/0.69 vs. 0.72/0.63 vs. 0.66; AUC: 0.77 vs. 0.83/0.80 vs. 0.85/0.76 vs. 0.86/0.70 vs. 0.76/0.70 vs. 0.69 RF/XG/ANN/TN/LR, respectively). The AI models outperformed LR when trained with the PS datasets. The important features shared after AI-driven feature selection in all models trained with the BL dataset included histopathological lymph node status (pN), histopathological tumor size (pT), clinical tumor size (cT), age at the time of surgery, and postoperative tracheostomy. Following training with the PS dataset with biomarkers, the important predictive features included patient age at the time of surgery, TP-53 gene mutation, Mesothelin expression, thymidine phosphorylase (TYMP) expression, NANOG homebox protein expression, and indoleamine 2,3-dioxygenase (IDO) expressed on tumor-infiltrating lymphocytes, as well as tumor-infiltrating Mast- and Natural killer cells. CONCLUSION: Different AI methods similarly predict the long-term survival status of patients with EC and outperform LR, the state-of-the-art classification model. Survival status can be predicted with similar predictive performance with patient data at an early stage of treatment when utilizing additional biomarker analysis. This suggests that individual survival predictions can be made early in cancer treatment by utilizing biomarkers, reducing the necessity for the pathological TNM status post-surgery. This study identifies important features for survival predictions that vary depending on the timing of oncological treatment.

Prospective Trial of Using Imaging to Predict Pathologic Response and Clinical Outcomes in Locally Advanced Esophageal Cancer

Trimodality therapy with chemoradiation (CRT) followed by esophagectomy is the standard of care for locally advanced esophageal cancer. An unresolved question is whether pathologic complete response (pCR) can be assessed non-invasively for patients post-CRT. In this study, we assessed whether diffusion-weighted imaging (DWI) with MRI or PET can be used as predictors of pCR and other clinical outcomes after CRT. Patients were enrolled on a single-arm institutional trial (PA13-0380) assessing the role of imaging in predicting outcomes in potentially resectable esophageal patients undergoing trimodality therapy. All patients received neoadjuvant CRT, and 29 patients had subsequent surgery. DWI MRI and PET scans were obtained at baseline, 2 weeks after the start of CRT (interim) and 4 to 6 weeks after completion of CRT (follow up). Apparent diffusion coefficients (ADCs) were calculated based on DWI images. Circulating tumor DNA was obtained for 27 patients post-radiation using CAPP-Seq. Mann-Whitney tests compared imaging changes associated with pCR. Discrimination of pCR by imaging changes was quantified by received operating characteristics. Youden's index was applied to select optimal thresholds. Kaplan-Meier analysis was performed to assess differences in overall survival (OS) and progression-free survival (PFS) by changes in DWI, PET, and ctDNA parameters. Our cohort of 60 patients had a median follow up of 42.7 months, age of 65.4 yrs, and ECOG of 1 at completion of CRT. 90% were male, 58% had a history of smoking, and 85% were white. 83% had adenocarcinoma with the rest squamous cell carcinoma. Stages of the patients ranged from IIA to IIIB. All had moderately (47%) or poorly (53%) differentiated disease. All received 41.4-50.4 Gy in 1.8 Gy fractions with the majority receiving 50.4 Gy (95%). 29 patients underwent surgery after CRT of which 8 (27.6%) had pCR. Mean ΔADC from baseline to mid-treatment was most associated with pCR (AUC = 0.98, p<0.001) for patients undergoing surgery. Max ΔADC from baseline to first follow-up was most associated with OS (p = 0.002) and PFS (p<0.001) for the whole cohort. 27 patients had ctDNA analyzed after RT with the presence of ctDNA significantly associated with worse OS (HR = 0.12, p = 0.05) and PFS (HR = 0.10, p = 0.002). Combining ctDNA and max ΔADC generated a model that was more predictive of OS and PFS than either alone. We found that neither the PET parameters of TLG or SUV max at baseline or changes in these parameters from baseline to mid-treatment or first follow-up were as predictive as DWI. We show that changes in DWI is associated with pCR, OS, and PFS in resectable esophageal cancer patients undergoing CRT. DWI was more predictive than PET and a model combining DWI and ctDNA was the most predictive of clinical outcomes. This study shows the significant promise of using DWI in potentially guiding treatment decisions in esophageal cancer patients and will require validation in a larger cohort.

Systemic treatments for resectable carcinoma of the esophagus.

One of the most prevalent malignancies in the world is esophageal cancer (EC). The 5-year survival rate of EC remains pitiful despite treatment advancements. Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease. The pathological complete response rate, however, is not acceptable. A distant metastasis or a locoregional recurrence will occur in about half of the patients. To increase the clinical effectiveness of therapy, it is consequently vital to investigate cutting-edge and potent therapeutic modalities. The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors. Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC, according to growing clinical data. A combination of chemotherapy, radiation, and immunotherapy may have a synergistic antitumor impact because, according to mounting evidence, these treatments can stimulate the immune system via a number of different pathways. In light of this, it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC. In this review, we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients, recap the clinical outcomes of these approaches, go through the upcoming and ongoing investigations, and emphasize the difficulties and unmet research requirements.

Preoperative neoadjuvant chemoradiotherapy provides borderline resectable thoracic esophageal cancer with equivalent treatment results as clinically T3 thoracic esophageal cancer.

Because the optimal treatment strategy for borderline resectable (cT3br) thoracic esophageal cancer patients remains unclear, it is of great interest whether preoperative neoadjuvant therapy for cT3br could achieve results comparable to those seen with resectable T3 cancer (cT3r). We speculated that preoperative neoadjuvant chemoradiotherapy (NACRT) would be particularly effective in cT3br thoracic esophageal cancer patients and compared to cT3br and cT3r. Of 186 cT3 thoracic esophageal cancer patients treated with intended NACRT, 162 received radical esophagectomy. More than 97% were squamous cell carcinomas. Patients were partitioned into two groups according to whether invasion of adjacent organs was suspected (cT3br and cT3r). Treatment outcomes and survival were analyzed. Sixty-eight patients (36.6%) were classified as cT3br and 118 (63.4%) as cT3r. The cT3br group had significantly more tumors in the upper and middle mediastinum (p < 0.0001) and more cases with cM1 (lymph node) (p = 0.0104) than the cT3r group. In addition, the cT3br patients receiving esophagectomy exhibited a significantly lower pathological complete response rate than the cT3r patients (p = 0.0374). However, the R0 resection rate did not differ between the cT3br and cT3r patients (p = 0.0978), and the two groups treated with intended NACRT had similar 5-year overall (OS) and disease-specific survival (DSS) (p = 0.3831 and p = 0.9020). In addition, the incidence and patterns of recurrence did not differ between the cT3br and cT3r patients receiving esophagectomy (p = 0.8109 and p = 0.3128). Preoperative neoadjuvant chemoradiotherapy appears to be a promising treatment for patients with borderline resectable thoracic esophageal squamous cell carcinoma.

The effectiveness of adjuvant treatment approaches for resectable esophageal cancer: A single-center experience.

In general, neoadjuvant treatment is the standard for clinical stage II/III esophageal cancer (EC), whereas the effect of adjuvant treatment on survival still remains controversial. The aim of this study was to investigate the efficacy of adjuvant treatment modalities on the survival of EC patients. A total of 63 patients with stage II-IVA EC who had undergone curative surgery between the years 2002 and 2020 were included in the study. Patients' data were retrospectively collected from oncologic follow-up files. Various treatment regimens were administered during this period, including chemotherapy and chemoradiotherapy. The median age was 56 years (24-73), and the number of males was slightly higher than females (male/female: 33/30). While 32 (51%) patients received postoperative adjuvant treatment, the remaining 31 (49%) patients underwent surgery alone. The median overall survival (OS) was 45.9 months (95% confidence interval [CI]: 25.1-66.8) in patients receiving adjuvant therapy and 37.6 months (95% CI: 20.9-54.4) in patients not receiving adjuvant therapy. The 8.3-month survival difference was statistically insignificant (P = 0.54). The 1-, 3-, and 5-year OS rates were 87.5% versus 77.4%, 58.4% versus 51.6%, and 40.8% versus 27.6% for patients with and without adjuvant therapy, respectively. Pathological stage (P = 0.028) and lymph node status (P = 0.044) were significant prognostic factors for survival. This study did not support the benefit of adjuvant treatment compared with surgery alone in completely resected EC patients. The reason for this result may be related to the small sample size and different treatment regimens due to the change in treatment options over time.

Quality of Life and Its Associated Factors in Patients After Esophagectomy at a Single National Referral Center

Introduction. Esophagectomy is the standard surgical treatment for resectable esophageal cancer patients. However, the success rate for this procedure was about 25–35% and was associated with a severe risk of postoperative complications. In addition, patients after esophagectomy have decreased their quality of life (QOL), but no research has been done in Indonesia. Therefore, this study was conducted to determine the quality of life after esophagectomy in Indonesia based on the patient population at Dr. Cipto Mangunkusumo General Hospital (CMGH).

462. IMPACT OF THE RATIO OF THE VISCERAL FAT AREA TO PSOAS MUSCLE AREA ON SURVIVAL FOR SURGICALLY RESECTED ESOPHAGEAL CANCER

Abstract Sarcopenia (the loss of skeletal muscle volume and/or quality) and obesity have received increasing attention in many malignancies because they are associated with postoperative complications and poor surgical outcomes. The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of the visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). A high V/P ratio was associated with higher age (p = 0.03), higher body mass index (BMI) (p&amp;lt;0.001), higher VFA (p&amp;lt;0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI &amp;lt; 25. A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

465. RELATIONSHIP BETWEEN THE PERIOPERATIVE NUTRITION, INFLAMMATION AND PROGNOSIS IN RESECTABLE ESOPHAGEAL CANCER PATIENTS, POSSIBLE SIGNIFICANCE OF NUTRITIONAL INTERVENTION

Abstract Inversed relationship between inflammatory response and nutrition were reported, and preoperative mGPS score has been proposed as a useful prognostic biomarkers in several malignancies. It has been reported that the postoperative inflammatory responses may cause cancer recurrence and metastasis. In the present study, we investigated the treatment strategy from perioperative inflammatory reaction and nutritional status in patients with resectable esophageal cancer. 110 esophageal cancer patients (Squamous cell carcinoma, Stage I / II / III / IV: 44/17/39/20) were evaluated. The preoperative mGPS score was evaluated on a scale of 0 to 2. The cut-off value of albumin, CRP were 3.5g/dl, 0.14mg/dl, respectively. As the postoperative CRP, CRPmax and the area under the CRP curve (CRP (7), CRP (14)) for 7 days and 14 days after the operation, and ROC curve was used to set at optimal cut-off value of these parameters. Outcome was RFS (Recurrence Free Survival) and identified prognostic factors were determined by Cox multivariate analysis. 1, Preoperative albumin value was significantly lower in high CRP (&amp;gt; 0.14mg / dl) (p &amp;lt;0.05)). 2, Preoperative mGPS score 0 was better RFS than in the other groups(p&amp;lt;0.05).3, Univariate analysis showed that mGPS, albumin, and CRP were prognostic factors for RFS, but Cox analysis showed mGPS was not prognostic factor. 4, The cut-off value of CRP (7) and CRP (14) were 59.9, 115.3, respectively. CRP (7) was prognostic factor for RFS in univariate analysis, but Cox analysis showed that only pStage and tumor locations were significant prognostic factors, high CRP (7) was tended to be poor prognostic (p = 0.089). Clinical Stages, tumor locations were most important prognostic factors in resectable esophageal cancer patients. However, preoperative nutritional intervention may improve the prognosis of patients with esophageal cancer if preoperative CRP values can be suppressed. Suppressing the inflammatory reaction one week after surgery may improve the prognosis of patients with esophageal cancer.

Linkage of time interval from neoadjuvant chemoradiotherapy to surgery with pathological response and survival profile in resectable esophageal cancer patients.

e16071 Background: The optimal time interval from neoadjuvant chemoradiotherapy (nCRT) to surgery remains controversial in esophageal cancer (ESC) patients. Hence, this study aimed to evaluate the relationship of the time interval from nCRT to surgery with the prognosis in ESC patients. Methods: Totally, 166 ESC patients treated with nCRT followed by surgical resection were reviewed. Their pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) were analyzed. Based on the median duration from nCRT to surgery, patients were classified into duration from nCRT to surgery ≥66 days group or &lt;66 days group. Results: The pCR rate was elevated in duration from nCRT to surgery ≥66 days group compared to &lt;66 days group (48.3% vs. 25.3%, P = 0.002), while DFS ( P = 0.316) and OS ( P = 0.883) were of no difference between these two groups. The duration from nCRT to surgery (≥66 days vs. &lt;66 days) (odds ratio (OR): 2.149, P = 0.039) was independently related to improved pCR rate as validated by multivariate logistic regression, while it did not correlate with DFS or OS (both P &gt; 0.05) by univariate and multivariate Cox’s regression analyses. Moreover, female gender ( P=0.001) and radiation dose ≥40 Gy. ( P = 0.039) could independently predict better pCR rate; and pCR rate was independently related to longer DFS ( P = 0.003) and OS ( P = 0.008). Conclusions: The prolonged time interval from nCRT to surgery relates to a higher pCR rate but does not correlate with DFS or OS in ESC patients.

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

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

Impact of the Ratio of Visceral Fat Area (VFA) to Psoas Muscle Area (PMA) (V/P Ratio) on Survival for Surgically Resected Esophageal Cancer.

The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), higher VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI < 25. A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

THE EMERGING ROLE OF IMMUNOTHERAPY IN GASTROESOPHAGEAL CANCER: STATE OF ART AND FUTURE PERSPECTIVE

The introduction of immunotherapy in the therapeutic algorithm of gastroesophageal cancer is still a debated issue. Recent findings from randomized clinical trials documented the efficacy of adjuvant nivolumab in improving disease free survival (DFS) in resectable esophageal and gastroesophageal junction cancer patients with residual pathologic disease after neoadjuvant chemoradiation (Check- Mate 577). Consistently, the … Continued

Real-world effectiveness and safety of camrelizumab-based neoadjuvant therapy in resectable esophageal cancer: Initial results of a prospective multicenter observational study.

250 Background: Camrelizumab, a fully humanized monoclonal anti-PD-1 antibody, has shown promising efficacy with good tolerance in neoadjuvant therapy of resectable locally advanced esophageal cancer (EC). The present study aimed to investigate the effectiveness and safety of camrelizumab-based neoadjuvant therapy in a comparatively larger number of resectable EC patients in a real-world setting and initial results were reported here. Methods: In this prospective multicenter observational study (ChiCTR2000039170), patients with histologically confirmed resectable EC who were scheduled for camrelizumab-based neoadjuvant therapy at the discretion of treating physicians/ oncologists were included. Eligible patients were aged ≥ 18 years, had ECOG PS of 0-1, measurable disease per RECIST v1.1, adequate organ function, and expected survival time of ≥ 3 months, as well as provided written informed consent. The primary endpoint was safety. The secondary endpoints were major pathologic response (MPR), pathologic complete response (pCR), R0 resection rate, overall response rate (ORR), one-year overall survival (OS) rate, and disease-free survival (DFS). Results: At total of 166 patients (62.9 ± 9.2 years, and 84.2% male) were enrolled between October 20 2020 and August 26 2021. All patients received neoadjuvant camrelizumab plus chemotherapies (primarily nab-paclitaxel and nedaplatin) except one receiving camrelizumab alone. Overall, 109 patients (65.7%) experienced treatment-related adverse events (TRAEs), most commonly reactive cutaneous capillary endothelial proliferation (RCCEP, 45.3%), cough (10.4%), and pneumonia (8.5%). Thirteen (7.8%) patients experienced grade 3-4 TRAEs. There was no grade 5 toxicity. At the data cutoff, 141 (84.9%) patients were evaluable for radiological response, 82 (69.5%) patients underwent surgical resection. The ORR was 70.9% (100/141) and the R0 resection rate was 97.5% (79/82). Among the 81 patients available for pathologic assessment, 51 (63.0%) patients achieved MPR and of which, 15 (18.5%) had pCR. The median survival times have not been reached at the time of data analysis. Conclusions: The real-world data of our resectable EC patients showed effectiveness and safety profiles of camrelizumab-based neoadjuvant therapy consistent with those observed in previous trials.

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

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

280 CONVERSION SURGERY FOR BORDERLINE T4 ESOPHAGEAL CANCER

Abstract Due to development of neo-adjuvant chemotherapy or chemoradiotherapy, the possibility of surgical resection for borderlint T4 esophageal cancer that seems difficult to resect is emerging. We retrospectively examine the effects of conversion surgery in patients for esophageal cancer as part of multidisciplinary treatment. Methods We undergo 364 cases esophagectomy between Jan 2011 and Dec 2018, and of the 10 cases were diagnosed as borderline resectable esophageal cancer patients at first admission. These 10 cases were undergone conversion surgery after chemotherapy. We retrospectively examined preoperative and postoperative treatment and their prognosis. Results The chemotherapy regimens given above 10 cases were DCF (4cases) and FP (6 cases). Borderline target organs: Aorta (4 cases), Left main bronchus(6 cases), LN invasion to pancreas (1 case). R0 surgery was achieved in 8 of 10 cases, and the pathological response was G1a: 5 cases, G1b: 2 cases, G2: 3 cases. The median number of lymph node metastases is 3 (0–19), with recurrence in 6 cases, and the median time to recurrence is 7 months (2–21 months). Treatment was performed in all 6 cases after recurrence. Four patients had radiation therapy, but their prognosis was severe: 2 cases survived and 4 cases died. Conclusion Conversion surgery as a multidisciplinary treatment still can not provide a satisfactory prognosis, so additional treatment strategies including radiation and more effective utilization of other modalities are expected.

Impact of chemotherapy on prognosis of resectable pathological T3N0M0 esophageal cancer patients: a population-based study.

Aims: This study aimed to retrospectively determine the influence factors and survival effects of chemotherapy in pathological T3N0M0 esophageal cancer (EC) patients based on histological type. Methods: A total of 1136 pathological T3N0M0 EC patients who had surgery were chosen from the Surveillance, Epidemiology and End Results database. The patients were divided into subgroups based on histological type and chemotherapy status. Multivariate logistic regression, log-rank test and Cox regression were used to identify prognostic risk factors and survival differences. A propensity score matching analysis was applied to adjust the covariates. The impact of additional chemotherapy was also assessed in patients who had postoperative radiotherapy. Results: The 5-year overall survival was 36.4% for all patients. Chemotherapy was an independent protective factor of survival in both adenocarcinoma and squamous cell carcinoma patients. In the survival analysis, chemotherapy significantly improved the prognosis of EC patients, both for adenocarcinoma and squamous cell carcinoma. Propensity score matching analysis validated these results. Conclusion: Chemotherapy is recommended for pathological T3N0M0 EC patients regardless of histological type.

Nivolumab for the treatment of esophageal cancer

ABSTRACT Introduction: Esophageal cancer (EC) is the seventh most common cancer and the sixth leading cause of cancer death worldwide. The prognosis for advanced EC patients remains poor and there are few effective therapeutic agents available. Nivolumab is a fully human IgG4 monoclonal antibody that exerts antitumor activity by inhibiting the interaction of programmed cell death protein 1 on activated lymphocytes with its ligands. Nivolumab monotherapy showed significant benefit for overall survival of patients with advanced esophageal squamous cell carcinoma (ESCC) relative to taxane as a second-line treatment. Additionally, adjuvant nivolumab monotherapy showed significant disease-free survival benefit relative to placebo for resectable EC patients with residual pathologic disease who had received neoadjuvant chemoradiotherapy followed by surgery. Areas covered: Here, we provide an overview of checkpoint blockade with nivolumab and present the available clinical data related to its use in EC. Expert opinion: Nivolumab should be the standard second-line treatment for advanced ESCC patients and possibly adjuvant treatment of choice after neoadjuvant chemoradiotherapy followed by surgery. Trials assessing efficacy of a combination of cytotoxic agents and nivolumab as first-line treatment, nivolumab-containing chemoradiotherapy, and neoadjuvant chemotherapy are ongoing. These trials should result in improved protocols for better clinical outcomes in EC.

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

The Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Esophageal Cancer Patients: A Systematic Review and Meta‐Analysis

Inconclusive results are available as to whether chemo/radiotherapy should be administered to resectable esophageal cancer patients before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy). The paper, via a meta-analysis of effects of treatment modalities when administering chemo/radiotherapy, aims to systematically evaluate the effect of timing of chemo/radiotherapy and surgery. We performed a systematic literature search for clinical trials of neoadjuvant and adjuvant therapy for patients with esophageal cancer. Using meta-analysis, we conducted direct and adjusted indirect comparisons of overall survival, complete resection rate (R0 resection), perioperative mortality, leakage rate and local recurrence in patients with resectable esophageal cancer. A total of 32 studies involving 7985 patients with esophageal cancer were included in the meta-analysis. Twenty-five randomized controlled studies indirectly compared neoadjuvant/adjuvant therapy with surgery alone, while five non-randomized controlled studies and two randomized controlled studies directly compared neoadjuvant with adjuvant therapy. Neoadjuvant therapy followed by surgery, compared with surgery along with adjuvant therapy, showed a significant overall survival advantage in our pooled analysis (HR 0.88; 95% CI 0.79-0.98). Directly compared with adjuvant therapy, neoadjuvant therapy demonstrated a lower local recurrence rate (OR 0.56; 95% CI 0.43-0.74) with low heterogeneity (I2 = 1%). Neoadjuvant therapy, comparing to surgery with or without adjuvant therapy, showed a significantly higher R0 resection rate (OR 2.86; 95% CI 2.02-4.04) with moderate heterogeneity (I2 = 38%) and no significant differences in postoperative anastomotic leakage (P = 0.50). However, neoadjuvant therapy, compared with surgery adjuvant therapy, significantly increased perioperative mortality in both direct and indirect comparisons (P < 0.01). We found that neoadjuvant therapy was associated with higher overall survival and R0 resection rate without increasing postoperative anastomotic leakage for patients with resectable esophageal cancer, whereas neoadjuvant therapy was associated with higher perioperative mortality after esophagectomy.

P44 THE EXTENT AND CONSEQUENCES OF LYMPHADENECTOMY IN ESOPHAGEAL CANCER SURGERY: A CASE VIGNETTE SURVEY

Abstract Background Lymph node dissection (LND) is part of standard operating procedure in resectable esophageal cancer patients regardless of lymph node status. The aim of this case vignette survey was to acquire expert opinions on current practice of LND, and to determine potential consequences of non-invasive lymph node staging on the extent of LND and postoperative morbidity. Methods An online survey including 5 short clinical cases (case vignettes) was sent to 272 esophageal surgeons worldwide. Extent of standard LND, potential changes in LND based on accurate lymph node staging and consequences for postoperative morbidity were evaluated. Results 86 esophageal surgeons (median experience in esophageal surgery of 15 years) participated in the survey (response rate 32%). Standard LND varied considerably between experts, for example pulmonary ligament, splenic artery, aortopulmonary window and paratracheal lymph nodes are routinely dissected in less than 60%. The omission of (parts of) LND is expected to decrease the number of chyle leakages, pneumonias laryngeal nerve pareses and reduce operating time. In order to guide surgical treatment decisions, a diagnostic test for lymph node staging after neoadjuvant therapy requires a minimum sensitivity of 92% and specificity of 90%. Conclusion This expert case vignette survey study shows that there is no consensus on the extent of standard LND. Esophageal surgeons seem more willing to extend LND rather than omit LND, based on accurate lymph node staging. The majority of surgeons expect that less extensive LND can reduce post-operative morbidity.