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Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune systems ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer.

Abstract Background The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA‐EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. Methods and Materials We identified 190 LA‐EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte‐related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. Results Median follow‐up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30) was linked to worse survival (HR: 1.013, 95% CI: 1.001–1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335–3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage‐IVA (p = 0.017), platelet‐to‐lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. Conclusion Higher doses of pericardial radiation might affect LA‐EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune‐checkpoint inhibitor treatment.

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Background: The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA‐EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. Methods and Materials: We identified 190 LA‐EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte‐related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. Results: Median follow‐up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30) was linked to worse survival (HR: 1.013, 95% CI: 1.001–1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335–3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage‐IVA (p = 0.017), platelet‐to‐lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. Conclusion: Higher doses of pericardial radiation might affect LA‐EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune‐checkpoint inhibitor treatment. [ABSTRACT FROM AUTHOR]

Purpose: Pathological complete response correlates with better clinical outcomes in locally advanced esophageal cancer (LA-EC). However, there is lack of prognostic markers to identify patients in the current setting of neoadjuvant chemoradiotherapy (NACRT) followed by surgery. This study evaluates the utility of mid-treatment diffusion-weighted imaging (DWI) in identifying pathological responders of NACRT. Methods: Twenty-four patients with LA-EC on NACRT were prospectively recruited and underwent three MRI (baseline, mid-treatment, end-of-RT) scans. DWI-derived apparent diffusion coefficient (ADC) mean and minimum were used as a surrogate to evaluate the treatment response, and its correlation to pathological response was assessed. Results: Mid-treatment ADC mean was significantly higher among patients with pathological response compared to non-responders (p = 0.011). ADC difference (ΔADC) between baseline and mid-treatment correlated with tumor response (p = 0.007). ADC at other time points did not correlate to pathological response. Conclusion: In this study, mid-treatment ADC values show potential to be a surrogate for tumor response in NACRT. However, larger trials are required to establish DW-MRI as a definite biomarker for tumor response. [ABSTRACT FROM AUTHOR]

Objective To compare the setup errors provided by the chest and abdomen flat frame fixation device and integral cervico-thoracic fixation device in supraclavicular regions of locally advanced esophageal cancer patients. Methods The cone beam computed tomography (CBCT) images of 50 patients with locally advanced esophageal cancer and received radiotherapy in supraclavicular region were retrospectively analyzed. The chest and abdomen flat frame fixation device (group A) or the integral cervicothoracic fixation device (group B) were used respectively with 25 in each.There were 175 CBCT images in group A and 230 CBCT images in group B. The setup errors of the two groups were analyzed, and the movement and displacement of acromioclavicular joint in three-dimensions were measured. The differences were compared by independent sample t test and rank sum test. Results The setup errors were significantly different between group A and group B. The P value in X axis (left-right) and Z axis (anterior-posterior) were both less than 0.001 (P＜0.001);The P value in pitch was less than 0.001 (P＜0.001)and roll was less than 0.05 (P＜0.05). The movement amplitude of acromioclavicular joint (ΔX, ΔY, ΔZ) of groups A and B were (0.10±0.10)cm and (0.08±0.08)cm in X axis, (0.14±0.13)cm and (0.11±0.11)cm in Y axis, (0.16±0.12)cm and (0.11±0.12)cm in Z axis. The three-dimensional displacement of groups A and B were (0.27±0.14)cm and (0.20±0.14)cm, (P＜0.001). Conclusions If the influence of rotation angle is well controlled, the application of the integral cervicothoracic fixation device is better to immobilize the acromioclavicular joint and reproduce the setup position for locally advanced esophageal cancer patients. Special attention should be paid for the influence of rotation angle on the location accuracy of target.

Abstract Background The treatment for the locally advanced esophageal cancer invading adjacent organs is controversial. We performed a radical surgery for a patient suffering from lower esophageal cancer with pancreatic invasion, and led to long-term survival. Case presentation A 62-year-old man with dysphagia, was endoscopically diagnosed lower esophageal cancer. Abdominal computed tomography shows that the tumor formed a mass with the solitary metastatic abdominal lymph node, which invaded pancreas body and gastric body. He was diagnosed locally advanced esophageal cancer cStage IIIC. As chemoradiotherapy was difficult because of the high risk of gastric mucosal damage, radical esophagectomy with distal pancreatectomy and reconstruction of gastric conduit were performed. The postoperative course was uneventful and the patient was discharged 16 days after operation. At present, 7 years after surgery, he is still alive with disease-free condition. Conclusion Esophagectomy with distal pancreatectomy may be feasible for locally advanced esophageal cancer with pancreatic invasion in terms of curability and long-term survival.

Objective: This study aimed to explore the efficacy of neoadjuvant chemotherapy plus programmed death-1 (PD-1) inhibitor camrelizumab for the treatment of locally advanced esophageal cancer., Methods: This was a retrospective analysis. 87 patients with locally advanced esophageal cancer were included who received neoadjuvant chemotherapy plus immunotherapy between June 2018 and April 2021 in our oncology department. The postoperative clinical outcomes and varying expressions of PD-1 were evaluated in all enrolled patients., Results: The post-treatment disease control rate (DCR) was 83.91%, and the objective response rate (ORR) was 59.77%. Cancer tissues were categorized based on PD-1 expression into PD-1 negative (39 cases) and PD-1 positive (33 cases), with a PD-1 positive rate of 45.83%. Patients with PD-1-positive tumors exhibited a significantly higher ORR compared to those with PD-1-negative tumors, although DCRs did not differ significantly between the groups. The 12-month progression-free survival rate was significantly higher in PD-1-positive patients. In contrast, no significant difference was found in the 12-month overall survival rate between the two groups. The incidence of grade III adverse events was 10.34%, and no grade IV or higher adverse events were observed., Conclusion: In patients with locally advanced esophageal cancer, neoadjuvant chemotherapy plus immunotherapy demonstrates good efficacy and safety, especially for PD-1-positive patients, and significantly improves prognosis., Competing Interests: None., (AJTR Copyright © 2024.)

Neo-adjuvant chemoradiotherapy (CRT) and perioperative chemotherapy are different strategies for treating non-metastatic esophageal cancer (EC). The advantages of neo-adjuvant therapies are primarily seen in patients who achieve a pathologic complete response (pCR) and therefore show higher survival rates and better prognosis. In general, less than one-third of patients with EC experience pCR after neo-adjuvant therapies; however, patients with esophageal adenocarcinoma (AC) demonstrate lower rates of pCR compared to those with esophageal squamous cell carcinoma (SCC), respectively. Herein, we describe two cases of locally advanced esophageal AC treated with cone-beam computed tomography (CBCT)-based online adaptive radiotherapy (ART) on the ETHOS platform. Both patients received CRT with 50.4 Gy in 28 fractions, combined with weekly carboplatin and paclitaxel. For each fraction, we evaluated scheduled and adapted plans using dose-volume histogram (DVH) data, and patients were treated with the superior plan. We prioritized ensuring optimal coverage of the planning target volume (PTV) over limiting the dose to organs at risk (OARs) when selecting the superior treatment plan. In this instance, we present the translation of superior dosimetric data into clinical benefits, as evidenced by an excellent pathologic response., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: We have planned a prospective trial as an investigator-initiated study with Varian. This study will include patients with esophageal cancer who are treated with online adaptive radiotherapy. In this submission, we report on two cases that are not related to the planned prospective trial., (Copyright © 2024, Bachmann et al.)

Abstract Esophageal cancer is one of the most commonly diagnosed malignant tumors, especially in north China. Surgery is one of the major treatments. However, for locally advanced cases, surgery alone does not achieve an ideal prognosis. As a result of rapid development in recent years, neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy followed by surgery are becoming the “standard treatment pattern” for patients with locally advanced esophageal cancer, and an improvement in prognosis is evident. With the gradual application of immunotherapy in esophageal cancer, neoadjuvant immunotherapy has also shown an important role. This article mainly focuses on the history and current status of neoadjuvant treatment and its future role in the treatment of esophageal cancer.

Purpose: A multidisciplinary treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) is required to achieve prolonged survival. We aimed to clarify the differences in treatment strategies for locally advanced ESCC and the outcomes of elderly (aged ≥ 75 years) vs. younger patients (aged < 75 years). Methods: We compared the treatment strategy selection and the outcomes of 40 elderly and 160 younger patients with cStage II/III ESCC diagnosed between January, 2014 and December, 2016. Results: Nineteen (47.5%) of the elderly patients and 144 (90.0%) of the younger patients underwent esophagectomy and 9 (22.5%) of the elderly patients and 131 (81.9%) of the younger patients received neoadjuvant chemotherapy. Ivor–Lewis or transhiatal esophagectomy was performed more frequently in the elderly group than in the younger group (P = 0.0096). The survival rate after esophagectomy was higher in the younger group than in the elderly group. The overall survival rate of the elderly patients who underwent esophagectomy was significantly higher than that in those who did not. Conclusions: Esophagectomy is a practical choice for elderly patients with locally advanced ESCC, although reduced treatment intensity may impact long-term survival. [ABSTRACT FROM AUTHOR]

Background: The treatment for the locally advanced esophageal cancer invading adjacent organs is controversial. We performed a radical surgery for a patient suffering from lower esophageal cancer with pancreatic invasion, and led to long-term survival. Case presentation: A 62-year-old man with dysphagia, was endoscopically diagnosed lower esophageal cancer. Abdominal computed tomography shows that the tumor formed a mass with the solitary metastatic abdominal lymph node, which invaded pancreas body and gastric body. He was diagnosed locally advanced esophageal cancer cStage IIIC. As chemoradiotherapy was difficult because of the high risk of gastric mucosal damage, radical esophagectomy with distal pancreatectomy and reconstruction of gastric conduit were performed. The postoperative course was uneventful and the patient was discharged 16 days after operation. At present, 7 years after surgery, he is still alive with disease-free condition. Conclusion: Esophagectomy with distal pancreatectomy may be feasible for locally advanced esophageal cancer with pancreatic invasion in terms of curability and long-term survival. [ABSTRACT FROM AUTHOR]

Chemoradiation therapy (CRT) of locally advanced esophageal cancer (LAEC), although improving outcomes of patients, still results in 50% of local failure. An early prediction could identify patients at high risk of poor response for individualized adaptive treatment. We aimed to investigate physiological changes in LAEC using diffusion and perfusion magnetic resonance imaging (MRI) for early prediction of treatment response. In the study, 115 LAEC patients treated with CRT were enrolled (67 in the discovery cohort and 48 in the validation cohort). MRI scans were performed before radiotherapy (pre‐RT) and at week 3 during RT (mid‐RT). Gross tumor volume (GTV) of primary tumor was delineated on T2‐weighted images. Within the GTV, the hypercellularity volume (VHC) and high blood volume (VHBV) were defined based on the analysis of ADC and fractional plasma volume (Vp) histogram distributions within the tumors in the discovery cohort. The median GTVs were 28 cc ± 2.2 cc at pre‐RT and 16.7 cc ± 1.5 cc at mid‐RT. Respectively, VHC and VHBV decreased from 4.7 cc ± 0.7 cc and 5.7 cc ± 0.7 cc at pre‐RT to 2.8 cc ± 0.4 cc and 3.5 cc ± 0.5 cc at mid‐RT. Smaller VHC at mid‐RT (area under the curve [AUC] = 0.67, P =.05; AUC = 0.66, P =.05) and further decrease in VHC at mid‐RT (AUC = 0.7, P =.01; AUC = 0.69, P =.03) were associated with longer progression‐free survival (PFS) in both discovery and validation cohort. No significant predictive effects were shown in GTV and VHBV at any time point. In conclusion, we demonstrated that VHC represents aggressive subvolumes in LAEC. Further analysis will be carried out to confirm the correlations between the changes in image‐phenotype subvolumes and local failure to determine the radiation‐resistant tumor subvolumes, which may be useful for dose escalation. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by vascular manifestations including mucocutaneous and visceral telangiectasias and arteriovenous malformations. Herein we present the case of a relatively young patient with HHT with an incidentally discovered locally advanced esophageal cancer on endoscopic screening and pathologically complete response after neoadjuvant chemoradiation. This case highlights an unusual tumor response to chemoradiation in locally advanced esophageal cancer, and the surveillance care of HHT patients.

Esophageal cancer is one of the most commonly diagnosed malignant tumors, especially in north China. Surgery is one of the major treatments. However, for locally advanced cases, surgery alone does not achieve an ideal prognosis. As a result of rapid development in recent years, neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy followed by surgery are becoming the "standard treatment pattern" for patients with locally advanced esophageal cancer, and an improvement in prognosis is evident. With the gradual application of immunotherapy in esophageal cancer, neoadjuvant immunotherapy has also shown an important role. This article mainly focuses on the history and current status of neoadjuvant treatment and its future role in the treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Thoracic surgeons have recognized the advantages of minimally invasive esophagectomy (MIE). However, MIE for locally advanced esophageal cancer after neoadjuvant chemoradiotherapy (NCRT) is controversial. This study aimed to nvestigate and summarise the reliability and safety of MIE after NCRT. Methods We retrospectively analyzed the perioperative outcomes of patients with locally advanced esophageal cancer who underwent minimally invasive esophagectomy after neoadjuvant chemoradiotherapy from January 2016 to January 2018, and compared them with patients who underwent MIE alone during the same period. Results In total, 107 patients were eligible for the study. Forty-four patients underwent MIE after NCRT (CRM), and 63 patients underwent MIE alone (MA). The surgical duration (253.59 ± 47.51 vs. 222.86 ± 42.86 min), intraoperative blood loss (164.55 ± 109.09 vs. 146.19 ± 112.89 ml), number of lymph nodes resected (18.36 ± 8.01 vs. 22.10 ± 12.03), duration of the postoperative hospital stay (12.84 ± 6.57 vs. 14.60 ± 8.48 days), postoperative intubation time (5.68 ± 3.08 vs. 6.54 ± 4.97 days), total incidence of complications (34.10% vs. 31.7%), and R0 resection rate (95.45% vs. 96.83%) had no significant difference. The incidence of arrhythmia was higher in CRM (P

Abstract Background The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. Methods A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Results Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. Conclusions When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by vascular manifestations including mucocutaneous and visceral telangiectasias and arteriovenous malformations. Herein we present the case of a relatively young patient with HHT with an incidentally discovered locally advanced esophageal cancer on endoscopic screening and pathologically complete response after neoadjuvant chemoradiation. This case highlights an unusual tumor response to chemoradiation in locally advanced esophageal cancer, and the surveillance care of HHT patients. [ABSTRACT FROM AUTHOR]

Background: In Japan, positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been covered by the national health insurance for esophageal cancer since 2006. FDG-PET is commonly performed in advanced esophageal cancer. The aim of this study was to determine the effect of FDG-PET on survival in patients with locally advanced inoperable esophageal cancer. Methods: We retrospectively reviewed all patients with cT4 and without M1 esophageal cancer on CT in our institution between 2000 and 2014, and data for 78 patients who meet the eligibility criteria described below were used for analysis in this study. The eligibility criteria included (1) cT4 esophageal cancer without distant metastases or M1 lymph node metastasis (UICC 2002), (2) histologically proven squamous cell carcinoma, (3) 20–79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with 50 Gy or more, and (6) no other active malignant tumor during treatment. Results: Two patients were excluded because abdominal lymph node metastases or neck lymph node metastases were detected by FDG-PET. In 78 eligible patients, FDG-PET was not performed before treatment in 41 of the 78 patients and was performed in the other patients. The median observation period was 68 months. The 3-year and 5-year overall survival rates in 78 patients were 36.9% and 30.8%, respectively. There was no significant difference in overall survival or progression-free survival between patients in whom FDG-PET was performed and those in whom FDG-PET was not performed (12.0 months vs. 11.0 months, p = 0.920 and 6.0 months vs. 6.0 months, p = 0.844, respectively). Conclusions: Compared with only CT, additional information from FDG-PET is not associated with improving survival in patients with locally advanced esophageal cancer. Our results suggest that FDG-PET might not have much meaning for survival in locally advanced esophageal cancer. [ABSTRACT FROM AUTHOR]

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 ( OR 0.73), female gender ( OR 0.81), Charlson-Deyo comorbidity score ≥2 ( OR 0.82), and high-volume centers ( OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 ( OR 0.79) and Clinical Stage III ( OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology ( OR 1.33) and nonacademic cancer centers ( OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 ( OR 0.15), female gender ( OR 0.80), and non-Caucasian race ( OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology ( OR 2.10) and high-volume centers ( OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment ( HR 0.49) to trimodality therapy ( HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of neoadjuvant chemoradiotherapy (NCRT) on perioperative immune function during surgery to treat resectable locally advanced esophageal cancer. Records were retrospectively analyzed for 220 patients with locally advanced esophageal cancer, of whom 112 received surgery alone and 98 received neoadjuvant NCRT plus surgery. The two groups were compared in terms of proportions of CD3+, CD4+, CD8+, and natural kill (NK) cells, as well as the ratio of CD4+ to CD8+ cells. These measurements were made using flow cytometry on preoperative day 1 and on postoperative days 1 and 7. Subgroup analysis were performed in terms of degrees of pathological response of NCRT. When the entire NCRT and no-NCRT (surgery alone) cohorts were compared, no significant differences in propocrtions of CD3+, CD4+, CD8+, or NK cells or in the CD4+/CD8+ ratio occurred at any of the three time points. Similar results were obtained using the subgroup of NCRT patients who were NCRT-sensitive, but the subgroup of NCRT-insensitive patients showed significantly lower CD4+ and NK proportions and lower CD4+/CD8+ ratio than the no-NCRT group.Our findings suggest that NCRT does not affect perioperative immune function in patients who are NCRT-sensitive, but it does significantly reduce such function in patients who are NCRT-insensitive. [ABSTRACT FROM AUTHOR]

Introduction: The goal of the current study was to investigate the predictive and prognostic values of repeated F-18 FDG PET/CT parameter changes for prediction of complete pathologic response (pCR) in patients with adenocarcinoma of locally advanced esophageal cancer (LAEC) who received preoperative concurrent chemoradiotherapy (PCRT).Methods: A total 53 patients with LAEC patients were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and during chemoradiotherapy. The percent changes (∆, %) in F-18 FDG PET/CT parameters were used to predict pCR and to calculate overall survival (OS). The predictive value for pCR of F-18 FDG PET/CT cutoff values was determined by ROC analysis. The prognostic significance was assessed using Kaplan-Meier analysis.Results: pCR occurred in 15 patients (28.3 %). When ΔSUVmax > 23.5 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 % and 52.6, respectively. The AUC was 0.750 (95 % CI; 0.612-0.859), and standard error (SE) was 0.0633 (p = 0.0002). ΔMTV resulted in 80 % sensitivity, 76.3 % specificity, and 0.731 AUC (95 % CI; 0.591-0.843, SE = 0.077, p = 0.0027) for cutoff values >25.5 %. When ΔTLG > 44.8 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 and 65.8 %, respectively. The AUC was 0.893 (95 % CI; 0.777-0.961), and SE was 0.0431 (p < 0.0001). Kaplan-Meier analysis showed that high ΔSUVmax, ΔMTV, and ΔTLG were associated with improved OS.Conclusion: In conclusion, the current study shows the capability of the changes (Δ) in repeated F-18 FDG PET/CT parameters to predict the achievement of pCR during PCRT in LAEC patients. Among the parameters, the ΔSUVmax, ΔMTV, and ΔTLG were predictors for pCR and well associated with OS. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to define the predictive values of preoperative Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) parameters and compared to define effective parameters for prediction of overall survival (OS) and recurrent free survival (RFS) in locally advanced esophageal cancer (LAEC).Materials and Methods: This study included 44 patients with LAEC who received F-18 FDG PET/CT. Univariate and multivariate analyses were used to calculate survival, and the survival curves were estimated by clinical factors and F-18 FDG PET/CT-derived parameters.Results: Higher values of F-18 FDG PET/CT parameters (SUVmax, SUVmean, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and advanced tumor-node-metastasis (TNM) staging showed higher mortality. The Cox proportional hazard regression model demonstrated advanced TNM stage and high MTV as poor OS factors. The early TNM stage, lower MTV, lower TLG, lymph node (LN) (-), and lower heterogeneity factor (HF) were also associated with better RFS. The MTV was the potent predictor for RFS.Conclusions: In conclusion, although the newly described parameter of HF measured by F-18 FDG PET/CT could be a prognostic factor, the MTV is the most potent prognostic predictor in LAEC. [ABSTRACT FROM AUTHOR]

Aims: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). Methods: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. Results: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. Conclusion: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose Neoadjuvant chemoradiotherapy is used prior to surgery in curative treatment of esophageal cancer (EC). We evaluated the in-field control of this multimodal treatment by extraction of radiation dose parameters and determination of the spatial relation between tumor recurrence location(s) and radiation target volume (RTV). Methods and materials Treatment consisted of neoadjuvant chemotherapy (5-FU and cisplatin) and radiotherapy (36 Gy) followed by Ivor–Lewis esophagectomy. For patients with locoregional recurrence(s), image fusion was performed between radiotherapy planning CT and follow-up CT(s). A region-of-interest was contoured on the planning CT around each locoregional recurrence. Mean and maximum radiation doses were then extracted to classify recurrences as out-of-field, marginal or in-field. Results Eighty patients were included. The median follow-up duration was 19 months. Fifteen of 95 locoregional recurrences were detected in the RTV. These in-field relapses occurred in only 6 patients (7.8%) on 12 different anatomical locations. None of the patients with in-field failure had a pCR and all had concurrent distant failure on multiple anatomical sites. Conclusion Neoadjuvant chemoradiotherapy followed by Ivor–Lewis esophagectomy yields excellent in-field control, as only a clear minority (7.8%) of patients developed a relapse in the RTV. In-field recurrence is associated with widespread tumor dissemination and poor pathological response to neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to evaluate if the F18-fluorodeoxyglucose positron emission tomography (F18-FDG PET) response after two weeks of chemoradiation for locoregionally advanced esophageal cancer (staged Tumor (T) 3 and/or Nodes (N)+ Metastases (M) 0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Materials and Methods Between March 2006 and September 2017, 40 patients were prospectively enrolled in our study, gave written consent, and had PET scans performed before treatment and after two weeks of chemoradiation. One patient did not undergo his two-week PET without informing study coordinators and was excluded from analyses. Results The median age at diagnosis was 62 years. Seventy-two percent of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, minor PET response, or good PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the positive predictive value (PPV) of the PET response relative to the pathologic response was 75% and the negative predictive value (NPV) was 62%. In study patients, the crude recurrence rate was 68% and there was no correlation between PET response and DFS. Conclusion In our study, interim PET response after two weeks of chemoradiation for locoregionally advanced esophageal cancer was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery)., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Lavertu et al.)

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post-therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194 and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194 and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression. [ABSTRACT FROM AUTHOR]

Loco-regionally advanced esophageal cancer is a lethal disease with poor outcomes despite aggressive multimodality therapy. The appropriate management of these patients is contentious and no single standard of care has been defined. Literature suggests that preoperative chemoradiotherapy may be superior to preoperative chemotherapy. Recently, several developments have impacted the care of these patients. The 2010 AJCC TNM staging system now recognizes the biologic heterogeneity of the disease and stages adenocarcinoma and squamous cell carcinoma separately. Studies suggest potentially less toxic chemotherapeutic agents including oxaliplatin may be useful in the management of this disease. FDG-PET imaging appears to have prognostic value and may predict for pathologic response. In addition, several trials have explored inhibition of the ErbB1 (EGFR) and ErbB2 (Her2) receptors. The monoclonal antibody trastuzumab appears to extend survival for patients with metastatic gastric and gastroesophageal junction adenocarcinoma and is under investigation for use in patients with loco-regionally advanced disease. [ABSTRACT FROM AUTHOR]

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A significant number of patients diagnosed with esophageal cancer will present with locally advanced disease. The appropriate management of these patients continues to be a matter of significant debate. Over the past 2 decades, concurrent chemoradiation has been widely recognized as a viable option for a majority of these patients. Although there have been no randomized trials comparing definitive chemoradiation with surgical resection, there is little doubt that nonoperative therapy offers comparative opportunity for cure with less intendent morbidity and mortality. The broad applicability of this treatment option has led investigators to study methods of maximizing the therapeutic gain associated with the combination of external beam radiation and systemic chemotherapy. The long-term survival results have compared favorably with surgical series, thus leading to clinical trials designed to define the role of surgery in future management strategies. The early evaluation of these recent trials fails to identify any significant advantage associated with the routine use of surgery for most patients. Recent advances in drug development in conjunction with the identification of specific molecular targets has provided new opportunities to improve on the outcomes achieved with standard chemoradiation combinations. [Copyright &y& Elsevier]

Purpose: From 1991 to 1994 we performed a phase II study with intensive preoperative chemoradiation in locally advanced squamous cell carcinoma and adenocarcinoma of the esophagus. We now report on a multivariate analysis of prognostic factors based on the long-term results at a median follow-up of 6.5 years. Patients and methods: Eighty-eight patients were treated. Prognostic factors for overall survival and local tumor control were identified by univariate and multivariate analysis. Results: Median overall survival reached 17 months, and the survival rate at 5 years was 22% (95%-confidence interval: 18-26%). Response to induction chemotherapy was the only independent factor predicting local tumor control and—beside weight loss prior to treatment—it also proved to be an independent prognostic factor for long-term survival. Conclusions: Intensive chemoradiation followed by surgery seems to be appropriate to improve long-term survival of high-risk patients with locally advanced esophageal cancer. In our trial, local tumor control and prognosis were best correlated with response to induction chemotherapy. These results may help to guide decisions regarding surgery in multimodal treatment of EC. Further efforts are needed to increase the number of treatment responders and to predict tumors not responding to chemo(radio)therapy earlier. [ABSTRACT FROM AUTHOR]

Purpose To determine the efficacy and toxicity of two standard chemotherapy regimens used concurrent with radiation for the treatment of esophageal cancer: cisplatin/5-fluorouracil (5-FU) and carboplatin/paclitaxel. Materials and methods We prospectively reviewed records of 364 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy (CRT) with or without resection. All patients received surgical evaluation and imaging at presentation as well as following completion of their course of CRT. Treatment and prognostic variables were compared across the two chemotherapy regimens. Results We identified 261 patients treated with concurrent carboplatin/paclitaxel (n = 133) or cisplatin/5-FU (n = 128). Weight loss during CRT was lower in patients receiving carboplatin/paclitaxel (median: 7.0 pounds; 4.1% body weight) vs. cisplatin/5-FU (median: 11.0 pounds; 6.5% body weight) (p < 0.01). In 117 patients receiving trimodality therapy, post-operative death rates within one month of resection were similar. Pathologic complete response was better with carboplatin/paclitaxel vs. cisplatin/5-FU, 29.6% vs. 21.8% (p = 0.03), respectively. In the multivariable analysis, there was no association between chemotherapy regimen and overall survival (OS) or progression-free survival (PFS), though there was a trend toward improved OS with carboplatin/paclitaxel with a HR = 0.75 (p = 0.08). Further analysis revealed that trimodality therapy and stage were predictors for improved OS and PFS while female gender and grade predicted for improved PFS. Conclusions Carboplatin/paclitaxel was associated with decreased weight loss and improved pathologic response for trimodality patients when compared to cisplatin/5-FU. We observed no differences in OS, PFS, or post-operative death by chemotherapy regimen for both the entire cohort and trimodality patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Steber et al.)

The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37-87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6-94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors.

Background: The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy., Methods: A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue., Results: Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart., Conclusions: When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Background/aim: Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy., Patients and Methods: Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m 2 , d1-4) and 5-FU (dose level 0: 500 mg/m 2 , dose level 1: 750 mg/m 2 , d1-4; dose level 2: 1,000 mg/m 2 , d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m 2 loading dose followed by 250 mg/m 2 weekly)., Results: At dose level 1 (n=3) and 2 (n=3), no patient experienced a dose-limiting toxicity. Minor treatment modifications were due to organization or request by physicians/patients. At dose level 2, only five grade 3 adverse events occurred., Conclusion: Dose level 2 appears safe and is used in a subsequent randomized phase II study., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study aims to evaluate the effect of neoadjuvant chemoradiotherapy (NCRT) on perioperative immune function during surgery to treat resectable locally advanced esophageal cancer. Records were retrospectively analyzed for 220 patients with locally advanced esophageal cancer, of whom 112 received surgery alone and 98 received neoadjuvant NCRT plus surgery. The two groups were compared in terms of proportions of CD3+, CD4+, CD8+, and natural kill (NK) cells, as well as the ratio of CD4+ to CD8+ cells. These measurements were made using flow cytometry on preoperative day 1 and on postoperative days 1 and 7. Subgroup analysis were performed in terms of degrees of pathological response of NCRT. When the entire NCRT and no-NCRT (surgery alone) cohorts were compared, no significant differences in propocrtions of CD3+, CD4+, CD8+, or NK cells or in the CD4+/CD8+ ratio occurred at any of the three time points. Similar results were obtained using the subgroup of NCRT patients who were NCRT-sensitive, but the subgroup of NCRT-insensitive patients showed significantly lower CD4+ and NK proportions and lower CD4+/CD8+ ratio than the no-NCRT group. Our findings suggest that NCRT does not affect perioperative immune function in patients who are NCRT-sensitive, but it does significantly reduce such function in patients who are NCRT-insensitive., (© 2016 International Society for Diseases of the Esophagus.)