Neoadjuvant Therapy For Esophageal Cancer Research Articles

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis.

The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.

Fecal Microbiota Transplantation Alleviates Severe PD-1 Inhibitor-Associated Colitis Caused by Neoadjuvant Therapy for Esophageal Cancer: A Case Report.

Surgical resection is the preferred treatment for early-stage esophageal cancer. But most patients with esophageal cancer are diagnosed at advanced stages, making them ineligible for surgery. Therefore, preoperative neoadjuvant therapy has been introduced to help them meet surgical requirements. However, this therapy has been associated with serious complications, such as diarrhea, preventing patients from surgery. During neoadjuvant therapy combined with chemoradiotherapy, a 58-year-old male patient with esophageal cancer was diagnosed with severe immune-related colitis, which seriously affected both cancer treatment and the patient's quality of life. Despite conventional antidiarrheal therapy, the patient remained refractory to treatment. However, after undergoing fecal microbiota transplantation, the frequency of diarrhea was significantly reduced. During e-colonoscopy, no significant ulcers were found in the sigmoid colon. Additionally, successful radical resection of esophageal cancer was performed, resulting in a favorable outcome for the patient. Regular follow-up appointments were scheduled to monitor the patient's progress. Fecal microbiota transplantation effectively relieved severe immune-related diarrhea in a patient undergoing neoadjuvant immunotherapy and chemoradiotherapy for esophageal cancer. This successful treatment ultimately enabled the patient to meet the surgical requirements for radical esophagectomy.

286. A BIBLIOMETRIC ANALYSIS OF NEOADJUVANT THERAPY FOR ESOPHAGEAL CANCER

Abstract Background The study aims to summarize publication characteristics of neoadjuvant therapy for esophageal cancer and create scientific maps to explore hotspots and emerging trends with bibliometric methods. Method The publications between 2013 and 2022 were retrieved from the Web of Science Core Collection (WoSCC) on March 4, 2023. Bibliometric tools including VOSviewer and CiteSpace were used for statistical analysis. Data on the trend of the annual output, countries/regions, institutions, journals, authors, subject categories, keywords, and co-cited references were presented in this study. Results A total of 1713 publications written by 9222 authors of 1696 institutions, 49 countries/regions in 287 journals were included in the bibliometric study. China was the most prolific country with 414 publications, and The United States was the country that cooperated most with other countries. Doki, yuichiro, van Hagen, p, annals of surgical oncology, j clin oncol, and sun yat sen univ were the top 1 productive author, co-cited author, productive journal, co-cited journal, and prolific institution, respectively. The top 4 most present keywords were esophageal cancer, neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and chemotherapy. Furthermore, the clinical research hotspots involved in the immunotherapy of ESCC have received the most attention in recent years. Conclusions This study visually analyzed the development status and scientific trend of neoadjuvant therapy for esophageal cancer over the past decade. The results could guide scientists to comprehensively understand the existing research and determine future directions. Keywords Web of Science (WOS); esophageal cancer; bibliometric analysis.

Anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome, and nedaplatin regimen for preoperative neoadjuvant therapy of esophageal cancer: A single-arm, single-center, phase II exploratory clinical study.

e16082 Background: Local recurrence and distant metastasis are important causes of high mortality in patients with locally advanced esophageal cancer. Neoadjuvant therapy combined with surgery can significantly improve the prognosis of patients with locally advanced esophageal cancer. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitors) and tislelizumab (anti-pd-1 antibodies), paclitaxel liposome (a cytotoxic anti-tumor drugs) and nedaplatin (a platinum-based anti-tumor drugs) in patients with esophageal cancer, to evaluate the efficacy and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin in preoperative neoadjuvant therapy for patients with stage IIB-IVA esophageal cancer. Methods: This study included 18-75 years old, ECOG PS 0-1 patients with potentially resectable stage IIB-IVA esophageal cancer with a predicted survival time of ≥12 weeks and confirmed by histopathology or cytology. Patients who met the inclusion criteria received anlotinib (oral, 12mg/d1-14,Q3W) combined with tislelizumab (intravenous drip, 200mg/d1,Q3W), paclitaxel liposome (intravenous drip, 175mg/m2/d1,Q3W) and nedaplatin (intravenous drip, 80mg/m2/d1,Q3W). After 2 cycles of neoadjuvant therapy, surgery was performed, and 4-6 weeks of chemotherapy combined with targeted immune adjuvant therapy was performed after the operation, and then Anlotinib combined with tislelizumab targeted immune maintenance therapy was performed until the disease progressed. Subjects who failed to complete at least one cycle of clinical trials according to this program due to non-experimental drug factors, and seriously violated this research program, such as: failure to follow the prescribed dose, method and course of medication, will be excluded from this study. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), R0 resection rate, and pathological complete response rate. Results: From October 2021 to February 2023, 38 patients were included in this study, and clinical data of 27 patients can be used to track and evaluate clinical efficacy. The median age of the subjects was 58.5 years (range 47-75 years). the primary study end point was an ORR of 77.8% (95% CI，61%-94.5%). Conclusions: We will strictly implement the research protocol and objectively evaluate the anti-tumor activity and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin regimen in the treatment of patients with stage IIB ~ IVA esophageal cancer. In order to provide a safe and reliable neoadjuvant therapy for patients with locally advanced esophageal cancer. Clinical trial information: ChiCTR2100049693 .

Neoadjuvant tislelizumab combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Single arm phase II study.

4068 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. Methods: This is a prospective single-arm clinical trial. A total of 20 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy (radiotherapy: 41.4Gy in 23 fractions; chemotherapy: Paclitaxel (Albumin bound) 100mg/m2, and Cisplatin 75 mg/m2 once every 3 weeks for 2 cycles.) Radical esophagectomy was performed within 4-6 weeks after neoadjuvant therapy. PET/CT was performed at baseline and before surgery. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immune biomarker to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. Results: Twenty patients enrolled, all of whom received neoadjuvant tislelizumab combined with chemoradiotherapy. Eighteen patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 18 patients who underwent surgery, R0 was 100% (18/18), 9 patients achieved pCR (50.0%), and 13 patients achieved MPR (72.2%). Most of treatment-related adverse event (TRAE) were grade 1-2, and the most common TRAE was anemia (15, 75.0%). The grade 3 TRAE included 1 leukopenia (5.0%), 1 neutropenia (5.0%), 1 liver damage (5.0%), and 1 elevated cardiac troponin T (5.0%). A significant decrease in SUVmax was observed in both pCR and no-pCR patients after treatment. Baseline SUVmax in no-pCR patients tended to be higher than pCR patients(p=0.0642). Furthermore, a significant increase in circulating CD4+ T cells, CD4+ effector memory T cells (TEM), and M1 were found after treatment. Among the patients with pCR, the CD4+ TEM and cDCs after treatment were higher than those in the no-pCR patients, while Tregs and M2 were lower. Conclusions: Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety. Clinical trial information: NCT05323890 . [Table: see text]

Prognostic implications of the extent of downstaging after neoadjuvant therapy for oesophageal adenocarcinoma and oesophageal squamous cell carcinoma

Abstract Background There are few data evaluating the extent of downstaging in patients with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma and the difference in outcomes for a similar pathological stage in neoadjuvant-naive patients. The aim of this study was to characterize the prognostic value of downstaging extent in patients receiving neoadjuvant therapy for oesophageal cancer. Methods Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma patients receiving either neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy between 2004 and 2017 were identified from the National Cancer Database. The extent of downstaging was defined as the extent of migration between groups (for example stage IVa to IIIb = one stage). Cox multivariable regression was used to produce adjusted models for downstaging extent. Results Of 13 594 patients, 11 355 with oesophageal adenocarcinoma and 2239 with oesophageal squamous cell carcinoma were included. In oesophageal adenocarcinoma, patients with downstaged disease by three or more stages (hazards ratio (HR) 0.40, 95 per cent c.i. 0.36 to 0.44, P < 0.001), two stages (HR 0.43, 95 per cent c.i. 0.39 to 0.48, P < 0.001), or one stage (HR 0.57, 95 per cent c.i. 0.52 to 0.62, P < 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses. In oesophageal squamous cell carcinoma, patients with downstaged disease by three or more stages had significantly longer survival than those with less downstaged disease, no change, or upstaged disease. Patients with downstaged disease by three or more stages (HR 0.55, 95 per cent c.i. 0.43 to 0.71, P < 0.001), two stages (HR 0.58, 95 per cent c.i. 0.46 to 0.73, P < 0.001), or one stage (HR 0.69, 95 per cent c.i. 0.55 to 0.86, P = 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses. Conclusion The extent of downstaging is an important prognosticator, whereas the optimal neoadjuvant therapy remains controversial. Identifying biomarkers associated with response to neoadjuvant regimens may permit individualized treatment.

Surgical intervention after neoadjuvant therapy in esophageal cancer: a narrative review.

Esophageal cancer is one of the common malignant tumors in China. Previous studies have shown that surgery alone is less effective. Neoadjuvant therapy refers to preoperative chemoradiotherapy, which is the standard treatment for locally advanced and operable esophageal cancer. Selection of appropriate surgical methods and timing after neoadjuvant therapy is of great significance for improving the prognosis of patients and reducing postoperative complications. An online electronic search of all eligible literature through PubMed, Google Scholar, and the Cochrane Library database was conducted using a combination of the following keywords: esophageal cancer, neoadjuvant therapy, neoadjuvant chemotherapy, chemoradiotherapy, immunotherapy, targeting, surgery, complications. With a focus on the use of surgery after neoadjuvant therapy, Eligible articles were identified by one or both authors. Neoadjuvant chemoradiotherapy combined with radical surgical resection remains the current standard of care for resectable esophageal cancer, significantly improving survival and pathologic complete response (PCR) compared with preoperative chemotherapy Recently, studies have also found that immunotherapy combined with chemotherapy has a more advantageous pathological response in patients with locally advanced disease. Although the emergence of targeted drugs has led to a change in treatment mode from traditional chemoradiotherapy to precision therapy, the postoperative progression-free survival (PFS) and overall survival (OS) need to be explored as well as how surgery-related risks caused by treatment can be reduced. Traditionally, surgery is performed 4-6 weeks after neoadjuvant therapy, and optimal timing for surgery after treatment is still being explored as research progresses, the surgical method also should be determined according to the specific situation of the patient. Postoperative complications should be dealt with in a timely manner, and of course, active preoperative intervention is equally important. Neoadjuvant therapy combined with surgery is the gold standard for resectable esophageal cancer. However, optimal timing of surgery after preoperative treatment remains unclear. Minimally invasive thoracoscopic surgery (including robotic surgery) has gradually replaced traditional open surgery. Active prevention before operation, accurate and meticulous operation during operation, and timely treatment after operation can minimize the incidence of adverse events.

Minimally invasive versus open esophagectomy after neoadjuvant therapy for esophageal cancer: a meta-analysis

ObjectivesNeoadjuvant therapy and minimally invasive esophagectomy (MIE) are widely used in the comprehensive treatment of esophageal cancer. This study aimed to investigate the advantages of MIE for esophageal cancer after neoadjuvant therapy.MethodsPublished clinical studies were reviewed and survival data and safety data were extracted. We compared the long-term survival and safety of MIE versus open esophagectomy after neoadjuvant surgery in a series of meta-analyses.Results6 retrospective studies were included. Overall, MIE could significantly improve the overall survival of patients with esophageal cancer after neoadjuvant therapy compared with open esophagectomy [hazard ratio (HR) = 0.86, 95% confidence interval (CI) (0.75, 0.98)]. Compared with open esophagectomy, MIE could significantly reduce intraoperative blood loss and operative time [mean difference (MD) = −40.28.78, 95% CI (− 62.98, − 17.58); MD = −28.78, 95% CI (− 42.48, − 15.07), respectively]. There was no significant difference in 30-day and 90-day mortality between MIE and open esophagectomy [odds ratio (OR) = 0.42, 95% CI (0.09, 2.01); OR 0.80, 95% CI (0.25, 2.60), respectively]. MIE could not significantly reduce the incidence of anastomotic leakage, recurrent laryngeal nerve palsy and chylothorax [OR 0.70, 95% CI (0.37, 1.32); OR 1.43, 95% CI (0.33, 6.25); HR = 1.79, 95% CI (0.67, 4.75), respectively], but the incidence of pneumonia was significantly reduced [HR = 0.43, 95% CI (0.22, 0.82)]. In addition, the length of hospital stay and the incidence of total complications were significantly reduced after MIE [MD = −2.61, 95% CI (− 3.10, − 2.12); HR = 0.66, 95% CI (0.45, 0.98), respectively].ConclusionMIE after neoadjuvant therapy is effective and safe. Compared with open esophagectomy, MIE can improve the long-term survival and reduce the incidence of postoperative complications of esophageal cancer patients.

Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma

Objectives2-deoxy-2[18F]Fluoro-d-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival.MethodsCohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy’s and St Thomas’ NHS Foundation Trust, London (2017–2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression.ResultsOptimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03–0.34; mTR HR 0.17 95% CI 0.06–0.48; pNR HR 0.17 95% CI 0.06–0.54; mNR HR 0.13 95% CI 0.02–0.66).ConclusionsMetabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival.Key Points• FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer.• Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection.• Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study.

Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer. However, there were few studies comparing nICT with nCRT. This study compared the efficacy and safety of nICT with that of nCRT administered prior to esophagectomy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). The study included patients with locally advanced resectable ESCC who were scheduled to receive neoadjuvant therapy at Gaozhou People's Hospital from January 1, 2019, to September 1, 2022. The enrolled patients were divided into 2 groups (nCRT or nICT) according to their neoadjuvant therapy regimen. The 2 groups were compared for their baseline data, the incidence of adverse events during neoadjuvant therapy, the clinical evaluation after neoadjuvant therapy, perioperative indicators, and the incidence of postoperative complications and postoperative pathological remission. A total of 44 patients were enrolled; 23 in the nCRT group and 21 in the nICT group. There were no significant differences between the 2 groups in the baseline data. In the nCRT group, leukopenia occurred more often than in the nICT group, and hemoglobin-decreasing events were rarer (P=0.03<0.05). A significantly higher proportion of patients in the nICT group experienced erythema following neoadjuvant therapy compared to the nCRT group (23.81% vs. 0%; P=0.01<0.05). Neoadjuvant therapy showed no significant difference between the 2 groups for adverse event rates, surgery-related indicators, postoperative pathological remission rates, and postoperative complications. nICT was a safe and feasible treatment for locally advanced ESCC and it may be a potential new treatment modality.

Risk Factors for Muscle Loss During Neoadjuvant Therapy for Esophageal Cancer.

In patients with esophageal cancer, muscle loss induced by neoadjuvant therapy before esophagectomy is correlated with poor prognosis. However, little is known about the causes of muscle loss. Thus, the purpose of this retrospective study was to clarify the risk factors for muscle loss during neoadjuvant therapy. Patients with esophageal cancer who underwent neoadjuvant therapy before esophagectomy between 2009 and 2020 were investigated (n=132). The patients received either cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin plus 5-fluorouracil (DCF); or CF with radiotherapy as neoadjuvant therapy. The cross-sectional areas of the bilateral psoas muscles were measured at the level of the third lumbar vertebra using CT, before and after neoadjuvant therapy, and psoas muscle loss was calculated. The patients were divided into the high muscle loss group with 5% or more muscle loss or the low muscle loss group with less than 5% loss. Correlations between muscle loss and clinical factors were evaluated. The median value of psoas muscle loss was 5.30%. Psoas muscle loss was significantly correlated with a poor 3-year overall survival rate (p=0.034). Multivariate analysis showed that the independent factors associated with muscle loss were age ≥70 years [odds ratio (OR)=2.43, p=0.022], treatment with DCF (OR=3.47, p=0.034), and a poor response to neoadjuvant therapy (OR=2.68, p=0.028). A regimen of DCF was a major trigger of muscle loss during neoadjuvant therapy.

Role of (F-18) Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Prediction of Response to Neoadjuvant Therapy in Esophageal Cancer: Correlation with Pathological Response and Survival.

The purpose of this study is to assess the correlation between metabolic response with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and pathological response in patients with locally advanced esophageal cancer treated with neoadjuvant chemoradiotherapy and to study FDG-PET parameters for the prediction of pathological response and outcome. Twenty-five patients with locally advanced esophageal cancer underwent two FDG-PET/CT scans for initial staging and after neoadjuvant chemoradiotherapy. FDG uptake in the primary tumor was calculated in both scans (SUVmax, SULpeak, and TLG). Metabolic response was assessed according to the reduction of PET parameters: complete response (mCR = 100%), partial response (mPR ≥50%), and no response (mNR ≤50%). Pathological response was also classified as complete (pCR), partial (pPR), or no response (pNR). Patients were followed up (range, 8-99 months) determining free-disease interval (FDI) and overall survival (OS). Two patients were excluded due to exitus for nonesophageal-related causes. The metabolic response was observed in 18/23 remaining patients (3mCR, 15 mPR), of which 12/18 patients showed a pathological response (3 pCR, 9 pPR). A major discrepancy was observed in 2 mNR patients who achieved pPR. FDI and OS were longer in patients with metabolic response than nonresponders, but no statistical difference was found. No significant correlation was found between PET parameters and pathological response, FDI, and OS. FDG-PET/CT is a useful technique to assess response to neoadjuvant chemoradiotherapy in esophageal cancer. Although in this preliminary study, no correlation between metabolic and pathologic response was found and no statistical differences between responders and nonresponders were observed, a tendency of longer FDI and OS was apparently found in responders patients.

OGC P22 The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer

Abstract Background Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Being able to predict which patients will respond to chemotherapy and chemoradiotherapy before they receive this treatment will prevent patients undergoing unnecessary procedures that may reduce their quality of life and help source alternative treatment options faster. This will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. Epigenetic mechanisms involving microRNAs that regulate gene expression during cancer have been implicated as a viable non-invasive potential solution to improving the accuracy of patient allocation to treatment. The expression levels of microRNAs within the body can change throughout the course of neoadjuvant therapy. In this study, we aim to determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. Methods A systematic review was conducted. Using the PICO framework focused research questions and inclusion and exclusion criteria were developed. Online databases MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies conducted from January 1st 1990 onward. The included studies investigated the expression of microRNAs taken before treatments to predict response to neoadjuvant therapy in patients with OAC and OSCC. Studies analysing OAC, OSCC or both together were considered separately. Quality and risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) assessment tool. Results 11,656 articles were identified, out of which 63 articles met the inclusion criteria and 15 were deemed eligible after full-text review. Across the 15 studies included in this systematic review, a panel of 20 microRNAs were identified as predictors of good or poor response to NAT. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response to NAT in OAC patients along with miR-193b in OSCC patients. This review has provided evidence suggesting that microRNAs may be robust biomarkers for predicting response to NAT by differentiating between responders and non-responders. However, the utilization of singular microRNAs to predict response to NAT is unlikely to be as sensitive or specific as looking at the microRNA expression profiles of multiple microRNAs. Conclusions The ability to predict OC in patients that will respond to NAT is vital to improve clinical outcomes whilst reducing treatment associated morbidity. MicroRNAs are valuable biomarkers of response to NAT in patients with OC. However, more research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardisation in how response is defined. Finally, validation studies are required to see the translation of such biomarkers in clinical practise.

Predicting Factors for a Favorable Pathologic Response to Neoadjuvant Therapy in Esophageal Cancer.

Favorable pathologic response(FPR) is a significant predictor for improved survival following Neoadjuvant therapy(NAT) in esophageal and gastroesophageal cancer(GEJ). Preoperative prediction of FPR could modify treatment plans. No reliable method for predicting FPR exists. We sought to identify preoperative predicting factors for FPR. Retrospective analysis of patients with esophageal and GEJ cancer who underwent esophagectomy following (NAT). Univariate and multivariate analysis was used to identify preoperative predicting factors for FPR. A comparison of Tumor Regression Grade(TRG) was used to assess treatment response on overall survival(OS). Out of 121 patients, 82(67.8%) had neoadjuvant chemoradiation. FPR was observed in 60(49.6%). Female sex, Radiation therapy(RT), squamous cell carcinoma(SCC), lack of signet ring feature, and FDG avidity posttreatment were associated with FPR on univariate analysis. RT and SCC were associated with FPR (OR=3.9 and 4.0, respectively) on multivariate analysis. OS was lower among patients who did not achieve FPR to NAT(P=0.027). FPR is a predictor of improved OS. SCC and radiation therapy-based protocol were identified as major prediction factors of FPR in patients with esophageal and GEJ cancers.

Impact of Diabetes on Pathologic Response to Multimodality Therapy for Esophageal Cancer

BackgroundThe incidence of esophageal cancer has increased faster than that of most cancers. Evidence from other malignant neoplasms suggests that diabetic patients have a worse response to multimodality therapy. We hypothesized that diabetic patients with esophageal cancer will have a decreased response to neoadjuvant chemotherapy and radiation therapy compared with nondiabetic patients. MethodsA retrospective study of The Society of Thoracic Surgeons General Thoracic Surgery Database identified all patients who had an esophagectomy after neoadjuvant therapy for esophageal cancer between 2012 and 2019. Patients were compared on the basis of the presence of diabetes. A pathologic complete response (pCR) was defined as ypT0 N0. The χ2 and Wilcoxon rank sum tests were used to compare patients’ demographic and clinical characteristics between those with and those without diabetes. Multivariable logistic regression was used to evaluate the predictors of response to neoadjuvant therapy. ResultsOf the 9171 patients who met inclusion criteria, 2011 (22%) patients were diabetic and 7160 (78%) patients were nondiabetic. Patients with diabetes were older, more likely to be male, and more likely to have all comorbidities. Univariate analysis revealed that diabetic patients were less likely to have pCR (16% vs 18%; P = .026). Although multivariable analysis showed a trend toward diabetic patients’ having lower odds of achieving pCR, diabetes was not independently associated with pCR (odds ratio, 0.89; 95% CI, 0.78-1.01; P = .075). ConclusionsDiabetic patients may be less likely than nondiabetic patients to achieve pCR after neoadjuvant treatment of esophageal cancer. This suggests the need for further exploration as diabetic patients with esophageal cancer can potentially benefit from different treatment paradigms compared with their nondiabetic counterparts.

Why is endosonography insufficient for residual diagnosis after neoadjuvant therapy for esophageal cancer? Solutions using muscle layer evaluation.

BACKGROUNDThe diagnosis of residual tumors using endoscopic ultrasound (EUS) after neoadjuvant therapy for esophageal cancer is considered challenging. However, the reasons for this difficulty are not well understood.AIMTo investigate the ultrasound imaging features of residual tumors and identify the limitations and potential of EUS.METHODSThis exploratory prospective observational study enrolled 23 esophageal squamous cell carcinoma patients receiving esophagectomy after neoadjuvant therapy [15 patients after neoadjuvant chemotherapy (NAC) and 8 patients after chemoradiotherapy (CRT)] at the Department of Surgery, Chiba University Hospital, between May 2020 and October 2021. We diagnosed the T stage for specimens using ultrasound just after surgery and compared ultrasound images with the cut surface of the fixed specimens of the same level of residual tumor. The ratio of esophageal muscle layer defect measured by ultrasound was compared with clinicopathological factors. Furthermore, the rate of reduction for the muscle layer defect was evaluated using EUS images obtained before and after neoadjuvant therapy.RESULTSThe accuracy of T stage rate was 61% (n = 14/23), which worsened after CRT (38%, n = 3/8) than after NAC (73%, n = 11/15) because of overstaging. Moreover, pT0 could not be diagnosed in all cases. The detection rate of residual tumor for specimens using ultrasound retrospectively was 75% (n = 15/20). There was no correlation between after-NAC (79%, n = 11/14) and after-CRT (67%, n = 4/6) detection rate. The detection of superficial and submucosal types was poor. The pathologic tumor size and pathological response were correlated. Tumor borders were irregular and echogenicity was mixed type after CRT. There was a correlation between the pT stage (pT0/1 vs pT2/3) and the length of muscle layer circumference (P = 0.025), the length of muscle layer defect (P < 0.001), and the ratio of muscle layer defect (P < 0.001). There was also a correlation between the pT stage and the rate of muscle layer defect reduction measured by EUS (P = 0.001).CONCLUSIONCompared to pathological images, some tumors are undetectable by ultrasound. Focusing on the esophageal muscle layer might help diagnose the depth of the residual tumor.

Current status and progression of minimally invasive surgery after neoadjuvant therapy for adenocarcinoma of esophagogastric junction

The number of minimally invasive surgery (MIS) for adenocarcinoma of esophagogastric junction (AEG) has been increasing year by year. The key technical points such as surgical approach, lymph node dissection and GI tract reconstruction have gradually reached their maturity. With the emergence of proofs of evidence-based neoadjuvant therapy, neoadjuvant chemotherapy or neoadjuvant radiochemotherapy for advanced AEG is also gradually accepted by most surgeons and oncologists. European scholars have previously started researches on MIS after neoadjuvant therapy for esophageal cancer and AEG. Domestic scholars also raise practical suggestions on the application of neoadjuvant therapy for AEG via the cooperation between gastrointestinal and thoracic surgeons, demonstrating the trend in standardization and individualization. But there is still no consent to the indication of MIS after neoadjuvant therapy. Furthermore, there is also a lack of the standardization of technical points for MIS, GI tract reconstruction, short- and long-term outcomes. Such associated problems have been the hot controversy and exploration in recent years. This article describes current progress of neoadjuvant therapy for AEG, current status of MIS after the neoadjuvant therapy in Europe, America, East Asia, including China, and related researches plus future prospects, hoping for better clinical outcomes.

The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer.

Simple SummaryChemotherapy and chemoradiotherapy are only effective in 25% to 30% of patients with oesophageal cancer. Being able to predict which patients will respond to chemotherapy and chemoradiotherapy before they receive this treatment will prevent patients undergoing unnecessary procedures that may reduce their quality of life and help source alternative treatment options faster. The scope of this review was to understand whether microRNAs, small non-coding RNA molecules that regulate gene expression, can be used as biomarkers to predict a patient’s response to chemotherapy and/or chemoradiotherapy treatment. This review showed that a number of microRNAs may have the potential to predict response to chemotherapy and chemoradiotherapy alongside other pre-treatment features already used. More research is needed to translate the use of microRNAs as biomarkers of response to the clinical setting, as well as understanding the effects different types of treatment have on predictability.Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient’s response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined.

Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis

SummaryIntroductionThe prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer.MethodsAn electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant.ResultsEight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26–1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22–0.77; P = 0.005).DiscussionThe findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer.

Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%–30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.