How appropriate is treating patients diagnosed with advanced esophageal cancer with anticancer drugs? A multicenter retrospective cohort Spanish study.

AIM: To assess the appropriateness of systemic oncological treatments (SOT) provided to patients diagnosed with advanced esophageal cancer (EC) across a group of participating hospitals. METHODS: Multicenter, retrospective cohort study in five Spanish hospitals including newly confirmed advanced EC cases between July 1, 2014, and June 30, 2016, with a 5-year follow-up. RESULTS: We identified 157 patients fulfilling the inclusion criteria (median age: 65 years, 85.9% males). Most patients, 125 (79.6%) were treated at least with one active treatment, and 33% received two or more lines of SOT. The 1-, 2- and 5-year overall survival rates were 30.3% [95%CI: 23.8, 38.7], 14.0% [95%CI: 9.3, 21.0], and 7.1% [95% CI: 3.8, 13.1] respectively, and the median survival time 8 months (95% CI: 6, 19) for stages IIIb IIIc and 7 months (95% CI: 5, 9) for stage IV. Clinical stage, receiving more than one line of SOT, and treatment with radiotherapy accelerated the time to death (0.4, 0.9-, and 0.8-times shorter survival respectively, p < 0.05). Better performance status (ECOG < 2) extended survival time by 2.2 times (p = 0.04). Age < 65 years (OR 9.4, 95% CI 3.2, 31.4, p < 0.001), and being treated in one particular hospital (OR 0.2, 95% CI 0.0, 0.8, p < 0.01) were associated with the administration of two or more lines of SOT. Altogether, 18.9% and 9.0% of patients received chemotherapy in the last four and two weeks of life, respectively. Moreover, 2.5% of patients were prescribed a new line of chemotherapy during the last month of life. The proportion of all patients who did not have access to palliative care reached 29.3%, and among those who had access to it, 34.2% initiated it in the last month of life. CONCLUSION: A high proportion of advanced EC patients receive many treatments not based on sound evidence and they do not benefit enough from palliative care services. The most accepted appropriateness indicators point out that some of the analyzed patients could have been overtreated. This study provides important insights into the quality of care provided to advanced EC, and furthermore, for giving valuable insight and opportunities for improvement.

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings.

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 system's 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.

A Diagnostic Quandary: Carboplatin-Paclitaxel-Induced Stevens-Johnson Syndrome in a Rare Case of Carcinosarcoma of the Esophagus and Review of the Literature.

Sarcomatoid carcinoma of the esophagus, a mixed tumor comprising both carcinomatous and sarcomatoid components and known as carcinosarcoma, is a rare malignancy. Clinically and radiologically, it presents like other esophageal cancers. Here we discuss the case of a 69-year-old male patient with sarcomatoid carcinoma of the esophagus who developed Stevens-Johnson syndrome (SJS) after chemotherapy with carboplatin and paclitaxel. The patient was evaluated for dysphagia and odynophagia. He was initially misdiagnosed to have an esophageal polyp and underwent excision for the same. He presented with recurrent growth at the local site, with histopathological examination showing sarcomatoid carcinoma of the esophagus. After the development of paclitaxel-carboplatin-induced SJS, the patient was subsequently treated with palliative radiotherapy at the primary site for symptomatic relief. He underwent feeding gastrostomy as a supportive nutritional measure and was on best supportive care after a multidisciplinary tumor board discussion. Paclitaxel-carboplatin-induced SJS poses numerous diagnostic conundrums, on account of there being only one reported incident prior to this in literature, to the best of our knowledge. In this report, we explore the diagnostic and therapeutic predicaments associated with a rare disease that is under-reported and understudied in literature and delve into the various treatment modalities that can benefit the patients. The case also demonstrates the delicate balance between cancer chemotherapeutics and their Pandora's box of adverse effects.

Radiotherapy for Advanced Esophageal Cancer: from Palliation to Curation.

OPINION STATEMENT: Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy.

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.

Prognostic nutritional index predicts the prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, their efficacy is variable, and there are still no effective and convenient biomarkers to identify and assess their efficacy. In recent years, programmed cell death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and other commonly used biomarkers still cannot meet clinical needs. PNI is easy to obtain and its predictive value for the prognosis of immunotherapy has been confirmed in many cancer species, but the relationship between PNI and the efficacy of immunotherapy for esophageal cancer is still unclear. Therefore, this study aims to explore the predictive value of PNI in advanced esophageal cancer treated with ICIs. Methods: The clinicopathological features of 78 patients with advanced EC who received immunotherapy in the 900th Hospital of the Joint Logistics Team from September 2018 to May 2022 were retrospectively analyzed. The laboratory test results within 10 days prior to the start of ICI treatment were recorded, including absolute lymphocyte count and albumin (ALB) level. Meanwhile, the effects of pre-treatment prognostic nutritional index (PNI) and body mass index (BMI) on the overall survival (OS) and progression-free survival (PFS) in patients with advanced EC were analyzed. Results: The median age of the enrolled patients was 58 years, and 38 patients (48.7%) received second-or-later-line therapy. The median progression-free survival (mPFS) and median overall survival (mOS) were 7.4 months and 13 months, respectively. The mPFS and mOS were 8.8 months and 15 months, respectively, in the high baseline PNI subgroup, which were significantly higher than those in the low baseline PNI subgroup (4.7 and 8.2 months, respectively; both P<0.05). Multivariate regression analysis showed that low baseline PNI was an independent predictor of poor PFS [hazard studio (HR) =0.35, 95% CI: 0.14-0.85, P=0.020) and poor OS (HR =0.41, 95% CI: 0.17-0.99, P=0.047) and treatment line was an independent predictor of PFS. Baseline BMI was not significantly associated with prognosis. Conclusions: PNI is a simple and effective biomarker for predicting the prognosis of immunotherapy in patients with advanced EC, although further prospective studies are warranted.

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

BACKGROUND: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. RESULTS: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. CONCLUSION: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Utility of Mid-treatment DWI in Selecting Pathological Responders to Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Cancer.

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.

Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab.

BACKGROUND: In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy. METHODS: The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves. RESULTS: During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001). CONCLUSIONS: Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

Prognostic Assessment of Interim F18-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer Treated With Chemoradiation With or Without Surgery.

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).

Effect of modified esophagectomy perioperative technique resection for patients with locally advanced esophageal cancer (tumor length > 8 cm): initial experience in 45 cases.

BACKGROUND: Patients with locally advanced esophageal cancer with a lesion length greater than 8 cm (LCWEC) are prone to high mortality in a short time due to esophagotracheal fistula (ETF) and esophagoaortic fistula (EAF). We tried to explore a safe salvage surgical method during the perioperative period to maximize the resection of the tumor on the premise of safety and reconstruction of the alimentary tract to avoid early death due to ETF and EAF. METHODS: From December 2007 to November 2018, forty-five LCWEC patients were treated using the modified Wu's esophagectomy. Patient features, surgical techniques, postoperative complications, and pathology outcomes were analyzed. RESULTS: The average length of the tumors was 12.5 cm (range 8.1-22.5 cm), and the average transverse tumor diameter was 5.8 cm (range 4.5-7.8 cm). No complications like anastomotic leakage, anastomotic stenosis, chylothorax, delayed gastric emptying, vocal cord paralysis, dumping syndrome, and reflux were detected. The 30-day and in-hospital mortality rates were 0%. Complete (R0) resection was achieved in 38 (84.4%) cases. The resection margin rate of positive anastomosis was 0%. Until the death of the patients, no feeding failure due to gastrointestinal obstruction and early death due to ETF or EAF occurrence. During follow-up, the median time to death was 17.2 months for patients treated with surgery alone and 32 months for patients treated with postoperative multimodal treatment. CONCLUSION: The modified Wu's esophagectomy is a safe and feasible salvage surgical method for LCWEC resection.

Pembrolizumab Plus Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A Cost-Effectiveness Analysis.

INTRODUCTION: In 2021, KEYNOTE-590 (NCT03189719) showed that pembrolizumab plus 5-fluorouracil and cisplatin (PPF) has more benefits than 5-fluorouracil and cisplatin (PF) as a first-line regimen to treat individuals with advanced esophageal cancer. However, given that it is expensive, controversies over the value of using this compared to competitive strategies remain. Hence, we conducted a cost-effectiveness evaluation of pembrolizumab plus chemotherapy. METHODS: A Markov model was applied in evaluating the efficacy and cost of PPF and PF over a 7-year horizon and measured the health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The economic data included were relevant to patients in the USA and China. We also performed one-way and probabilistic sensitivity analyses to determine the uncertainties relevant to the model. Willingness to pay thresholds (WTP) of $150,000/QALY (USA) and $35,673/QALY (China) were used to calculate a probability for the cost-effectiveness of PPF. RESULTS: PPF yielded 0.386-0.607 QALYs (0.781-1.195 LYs) compared with PF. In our analysis, compared with receiving PF, patients with advanced esophageal cancer receiving PPF had an ICER of $577,461/QALY in the USA and $258,261/QALY in China, those for esophageal squamous cell carcinoma were $550,211/QALY in the USA and $244,580/QALY in China, and a programmed cell death ligand 1 combined positive score (PD-L1 CPS) ≥ 10 was associated with a cost of $479,119/QALY in the USA and $201,355/QALY in China. Sensitivity analysis found the price of pembrolizumab to be the biggest influence. CONCLUSION: From the economic perspectives of the USA and China, a first-line regimen of PPF for esophageal cancer therapy may not be as cost-effective as PF. However, patients with esophageal cancer and PD-L1 CPS ≥ 10 may gain the most LYs from initial PPF treatment.

Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

PURPOSE: Few studies have reported the impact of chemoradiotherapy (CRT) on the objective response of patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the factors predicting therapeutic effectiveness and the short- and long-term outcomes in patients with T4b ESCC treated with CRT. METHODS: We included 155 patients with T4b ESCC who underwent CRT at the Department of Surgery, Gastroenterological Center, Yokohama City University, between January 2000 and December 2018. Responders were defined as patients who demonstrated a complete response (CR) or partial response (PR). Multivariate analysis for objective response was performed using a logistic regression model, and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: Among the 155 patients included, 20 and 84 patients demonstrated a CR and PR, respectively, resulting in a response rate of 67.1%. The median overall survival (OS) was 15.2 months, and the 3-year survival rate was 32.1%. High Glasgow prognostic score (GPS) and advanced N-category independently predicted the objective response to CRT. GPS and objective response were independent prognostic factors for OS. There was no significant difference in the long-term survival of responders who received subsequent chemotherapy or salvage surgery. CONCLUSIONS: High GPS and advanced N-category predicted a poor objective response to CRT in patients with T4b ESCC. Therefore, chemotherapeutic regimens with a higher efficacy are required. The indications for salvage surgery for responders should be carefully considered, with care taken to avoid complications. To confirm this, prospective randomized controlled studies are necessary.

Sequential chemotherapy after definitive radiotherapy in markedly elderly patients with advanced esophageal cancer.

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for advanced esophageal cancer, but it may be more invasive in the elderly and definitive radiotherapy (RT) alone may be selected. This study assessed the significance of sequential chemoradiotherapy (SCRT) in elderly esophageal cancer patients. Methods: We reviewed 87 patients aged 75 years and older, who were treated using definitive radiotherapy without concurrent chemotherapy for esophageal cancer. A total dose ranging from 50.4 to 63 Gy (median, 58.8) was delivered to the primary lesion and the involved lymph nodes. This study compared patients who received SCRT with those who received RT alone among 40 patients with stage III or IVA cancer. Descriptive statistics were calculated using Cox proportional hazards regression analysis and the generalized Wilcoxon test. Results: The total progression-free survival (TPFS), progression-free survival outside the irradiation field, and overall survival were significantly longer after SCRT (n = 15) than after definitive RT alone (n = 25; P = 0.0041 and 0.0098), whereas the progression-free survival in the irradiation field was not significantly different between the two groups. The TPFS was significantly shorter in patients who received RT alone than in those who received SCRT (P = 0.0372). There were no grade 4 or higher adverse events in the patients who received SCRT. Conclusion: SCRT was associated with a reduced relapse rate, suggesting that it should be considered for markedly elderly patients with advanced esophageal cancer.

Treatment strategies and outcomes for elderly patients with locally advanced squamous cell carcinoma of the esophagus.

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.

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study.

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

Comparison of Clinical Outcomes between Salvage and Elective Thoracic Endovascular Aortic Repair in Patients with Advanced Esophageal Cancer with Aortic Invasion: A Retrospective Cohort Study.

Aortoesophageal fistula (AEF) caused by esophageal cancer (EC) is a rare but life-threatening complication. However, the optimal management strategy remains undetermined. Previous cases have demonstrated that thoracic endovascular aortic repair (TEVAR) is effective for prophylactic management. In our study, we evaluated the management of AEF with elective TEVAR over salvage TEVAR. In our single-center retrospective cohort study, forty-seven patients with cT4M0 EC were included in this study, and we divided them into salvage (Group S) and elective (Group E) groups based on whether TEVAR was performed before the hemorrhagic AEF occurred. Our study outcomes included survival and complication rate after TEVAR. Group E showed better overall 90-day survival and aortic-event-free survival in 90-day and 180-day over Group S. More patients in Group E could receive subsequent chemoradiotherapy or esophagectomy. Significantly fewer AEF-related complications, including recurrent hemorrhagic events after TEVAR, hypoperfusion-related organ injury, and bloodstream infection, were noted in Group E. In patients with advanced EC-invading aorta, elective TEVAR offered an early overall and aortic-event-free survival benefit compared to salvage TEVAR. By reducing the AEF-related complications, elective TEVAR could provide more patients receiving subsequent curative-intent treatment.

Long-term survival after esophagectomy with distal pancreatectomy for locally advanced esophageal cancer with pancreatic invasion: a case report.

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.

Efficacy and Safety of Programmed Cell Death 1 Inhibitor Monotherapy Versus Chemotherapy as Second-Line Treatment for Advanced Esophageal Cancer: A Meta-analysis and Systematic Review.

PURPOSE: With programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC. METHODS: Eligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated. FINDINGS: The study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71-0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36-3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76-1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09-0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16-0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01). IMPLICATIONS: The available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients.

Prediction of the effects of radiation therapy in esophageal cancer using diffusion and perfusion MRI.

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.