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Background: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy., Patients and Methods: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection., Results: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40)., Conclusion: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival., (© 2024. The Author(s).)

Background: At the first interim analysis of the KEYNOTE-671 trial, adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival in participants with early-stage non-small-cell lung cancer (NSCLC). We report overall survival and health-related quality of life outcomes from the second interim analysis., Methods: KEYNOTE-671 was a global phase 3 trial done at 189 medical centres. Eligible participants (aged ≥18 years) with resectable stage II, IIIA, or IIIB (N2) NSCLC were randomly assigned (1:1) to four cycles of neoadjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant pembrolizumab (200 mg administered intravenously every 3 weeks) or to four cycles of neoadjuvant placebo (administered intravenously every 3 weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant placebo (administered intravenously every 3 weeks). Randomisation was done centrally using an interactive response technology system and was stratified by disease stage, PD-L1 expression, histology, and geographical region in blocks of four. Participants, investigators, and sponsor personnel were masked to treatment assignments; local pharmacists were unmasked to support treatment preparation. The dual primary endpoints were overall survival and event-free survival evaluated in the intention-to-treat population. This study is registered at ClinicalTrials.gov, NCT03425643, and is ongoing but closed to enrolment., Findings: Between May 11, 2018, and Dec 15, 2021, 797 participants were randomly assigned to the pembrolizumab group (n=397) or the placebo group (n=400). Median study follow-up at the second interim analysis was 36·6 months (IQR 27·6-47·8). 36-month overall survival estimates were 71% (95% CI 66-76) in the pembrolizumab group and 64% (58-69) in the placebo group (hazard ratio 0·72 [95% CI 0·56-0·93]; one-sided p=0·0052; threshold, one-sided p=0·0054). Median event-free survival was 47·2 months (95% CI 32·9 to not reached) in the pembrolizumab group and 18·3 months (14·8-22·1) in the placebo group (hazard ratio 0·59 [95% CI 0·48-0·72]). In the as-treated population, grade 3-5 treatment-related adverse events occurred in 179 (45%) of 396 participants in the pembrolizumab group and in 151 (38%) of 399 participants in the placebo group. Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group and three (1%) participants in the placebo group., Interpretation: The significant overall survival benefit of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone coupled with a manageable safety profile support the use of perioperative pembrolizumab in patients with resectable, early-stage NSCLC., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., Competing Interests: Declaration of interests JDS, MCG, HW, ML, TK, MT, S-HL, K-NC, CD, MM, EE, GLM, OB, DR-A, JEC, SN, and SG report funding to their institution from Merck Sharp & Dohme (MSD), a subsidiary of Merck & Co, Rahway, NJ, USA to support conduct of this study. JDS, MCG, HW, ML, TK, MT, S-HL, K-NC, CD, MM, EE, GLM, OB, DR-A, JEC, SN, JY, AA, SMK, AS, and SG received medical writing and editorial support for the preparation of this manuscript from MSD. JDS additionally reports receiving grants to the institution from AstraZeneca, MSD, Roche, BMS, CLS Therapeutics, Protalix Biotherapeutics, Pfizer, and Regeneron; receiving consulting fees from AstraZeneca, Merck, Roche, BMS, Novartis, Chemocentryx, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai, and Pfizer; receiving payment for a speaking role from Peerview, OncLive, and Medscape; receiving support for attending meetings or travel from AstraZeneca, Merck, and BMS; participating on a clinical trial safety monitoring board for AstraZeneca; and receiving equipment, materials, drugs, gifts, or other services via grant to the institution from Roche, MSD, BMS, and AstraZeneca. MCG additionally reports receiving consulting fees from AstraZeneca, Abion, MSD International, Bayer, BMS, Boehringer Ingelheim Italia, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi-Sankyo, Regeneron, Merck & Co, Blueprint, Janssen, Sanofi, AbbVie, BeiGene, Oncohost, Medscape, Gilead, Io Biotech, and Revolution Medicines; receiving payment or honoraria for lectures, presentations, speakers' bureaus, or educational events from AstraZeneca, Merck & Co, Daiichi Sankyo, Gilead, Eli Lilly, and Regeneron; and receiving support for attending meetings or travel from AstraZeneca. HW additionally reports research funding to the institution from Bayer, AstraZeneca, BMS, Genentech/Roche, MSD, Helsinn, SeaGen, and Xcovery; serving as a compensated advisory board member for Mirati, IOBiotech, OncoC4, and BeiGene; serving as an uncompensated advisory board member for MSD, Genentech/Roche, BMS, and AstraZeneca; serving as a past president of the International Association for the Study of Lung Cancer (IASLC); and serving on the executive committee of ECOG-ACRIN. TK additionally reports research grants to the institution from AbbVie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, and Takeda; receiving honoraria for lectures, presentations, speakers' bureaus, or educational events from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda; receiving honoraria for participation on a data safety monitoring board or advisory board from AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Janssen, Merck KGaA, MSD, Novartis, and Pfizer; and having a spouse who is an employee of Eli Lilly. MT additionally reports research grants to the institution from MSD, AstraZeneca KK, Bristol-Myers Squibb KK, Ono Pharmaceutical Co, Eli Lilly Japan, Novartis, MiRXES, and Johnson & Johnson Japan; receiving honoraria for lectures from Amgen KK, Johnson & Johnson Japan, Medtronic Japan, AstraZeneca KK, Eli Lilly Japan, Chugai Pharmaceutical Co, Taiho Pharma, Bristol-Myers Squibb KK, Ono Pharmaceutical Co, Novartis, MSD, and Daiichi-Sankyo; serving as a participant on an advisory board for Bristol-Myers Squibb KK, AstraZeneca KK, MSD, Novartis, and MiRXES; and serving as a participant on a data safety monitoring board for Chugai Pharmaceutical Co. S-HL additionally reports research grants to the institution from MSD and receiving honoraria for a lecture from MSD. MM additionally reports receiving honoraria for lectures, presentations, speakers' bureaus, or educational events from MSD, Lilly, Pfizer, AstraZeneca, Roche, Sanofi, Regeneron, BeiGene, Immedica, Novartis, and BMS; and receiving support to attend meetings or travel from MSD, Pfizer, AstraZeneca, and Roche. EE additionally reports receiving payment for expert testimony from MSD. OB additionally reports support for attending meetings or travel from MSD for ASCO 2023 and from AstraZeneca for ESMO 2023 and ASCO 2024; and participating as a compensated advisory board member for BMS, Roche, Takeda, MSD, AstraZeneca, Janssen, and MSD. DR-A additionally reports receiving honoraria for lectures from MSD, Roche, BMS, Novartis, Takeda, Lilly, and AstraZeneca; receiving support for attending meetings or travel from Roche, MSD, Novartis, and Sanofi; and participation on an advisory board from MSD, Regeneron, BMS, GSK, and Lilly. JEC additionally reports receiving research grants to the institution from AstraZeneca, BMS, Novartis, Genentech, Merck & Co, and BeiGene; and receiving consulting fees from AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Genentech, Merck & Co, Regeneron-Sanofi, Janssen, Guardant Health, Flame Biosciences, and Roche. SN additionally reports receiving honoraria for lectures, presentations, speakers' bureaus, or educational events from AstraZeneca, Amgen, BeiGene, Pfizer, MSD, Sanofi, Takeda, Thermo Fisher, Janssen, Novartis, and Roche; and participating on a data safety monitoring board or advisory board from AstraZeneca, Amgen, BeiGene, Pfizer, MSD, Sanofi, Takeda, Janssen, and Roche. JY additionally reports receiving salary for full-time employment from MSD. AA, SMK, and AS additionally report receiving salary for full-time employment from MSD and holding stock in Merck & Co, Rahway, NJ, USA., (Copyright © 2024 Elsevier Ltd. 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Background: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone., Methods: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety., Results: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events., Conclusions: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.)., (Copyright © 2023 Massachusetts Medical Society.)

Importance: Safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence., Objective: To compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC., Design, Setting, and Participants: A prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020., Interventions: Eligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups., Main Outcomes and Measures: The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life., Results: Among 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, -8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24)., Conclusions and Relevance: Initial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC., Trial Registration: ClinicalTrials.gov Identifier: NCT03001596.

Purpose: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR ) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results., Methods: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR -activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data., Results: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively., Conclusion: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Purpose: To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced EGFR mutation-positive non-small-cell lung cancer., Patients and Methods: This was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer with EGFR mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m 2 plus cisplatin 75 mg/m 2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability., Results: Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84; P = .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67; P < .001). Observed adverse events reflected those most commonly seen with the two treatments., Conclusion: The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.

Background: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC., Methods: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m 2 on days 1 and 8) plus intravenous cisplatin (75 mg/m 2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079., Findings: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related., Interpretation: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature., Funding: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling., Methods: CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo-responsiveness., Results: EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively., Conclusions: MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

Background: Accurate prediction of treatment response and prognosis before surgery allows prompt therapy adjustment. This study aimed to evaluate the efficacy of computed tomography (CT) signs in predicting treatment response and survival for advanced esophageal squamous cell carcinoma patients who received preoperative chemotherapy., Methods: This study retrospectively enrolled 135 consecutive patients with preoperative chemotherapy from September 2005 to December 2011. A logistic regression model was used to evaluate the association between pathologic response and CT signs. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and a Cox proportional hazards model was constructed to determine associations between CT signs after neoadjuvant chemotherapy and survival outcomes., Results: Logistic regression showed that the significant predictors of a poor response were the total number of lymph nodes (LNs) (>6) at baseline [odds ratio (OR) 5.07; 95 % confidence interval (CI) 1.86-13.81; P = 0.002] and the CT value change rate (≤17 %) (OR 2.35; 95 % CI 1.05-5.23; P = 0.037). In the Cox analyses, the significant predictors of OS were preoperative tumor thickness (>10 mm) [hazard ratio (HR) 2.33; 95 % CI 1.36-4; P = 0.002), total number of LNs (>6) (HR 1.88; 95 % CI 1.12-3.17; P = 0.017), and short diameter of the largest LN (>10 mm) (HR 1.87; 95 % CI 1.07-3.28; P = 0.028), whereas only the short diameter of the largest LN was a significant predictor of DFS (HR 2.36; 95 % CI 1.23-4.54; P = 0.01)., Conclusions: CT signs can predict therapeutic efficacy and survival outcomes and provide an opportunity to offer additional treatment options before surgery.