Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer.
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ABSTRACT:
SUBMITTER: Wong C
PROVIDER: S-EPMC5538970 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:The optimal treatment for locally advanced esophageal squamous cell carcinoma remains unclear. We compared the clinical outcomes of neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy [the surgery group] and CCRT without surgery [the CCRT group] in patients with squamous cell carcinoma from an Asian population. METHODS:Eligible patients diagnosed from 2008 to 2015 were identified through the Taiwan Cancer Registry. To balance observable potential confounders, we constructed a 1:1 propensity score-matched cohort [surgery vs CCRT]. We compared the hazard ratios between the surgery and CCRT groups for death using a robust variance estimator. We also evaluated the outcomes of patients for freedom from local regional recurrence (FFLRR) and esophageal cancer-specific survival (ECSS). Extensive supplementary analyses were performed to examine the robustness of our findings. RESULTS:Our study population included 298 patients balanced with respect to the observed covariables. The hazard ratio of death was 0.56 [95% confidence interval 0.42~0.75] when surgery was compared to CCRT. The results remained significant in the FFLRR and ECSS outcomes. In the supplementary analyses, our results also remained significant when additional covariables were taken into consideration or when the definition of the index date was changed. CONCLUSIONS:When compared to definitive CCRT, neoadjuvant CCRT followed by esophagectomy was associated with improved overall survival for locally advanced esophageal squamous cell carcinoma. However, given the nonrandomized nature of the study and the sensitivity to potentially unmeasured confounders, our results should be interpreted cautiously.
| S-EPMC6046100 | biostudies-literature
Project description:BackgroundProgrammed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC.MethodsFrom July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes.ResultsA total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients.ConclusionsnCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined.Trial registration numberNCT04437212.
| S-EPMC10921522 | biostudies-literature
Project description:The study aimed to investigate the clinical significance of interim response evaluation during definitive chemoradiotherapy (dCRT) in predicting overall treatment response and survival of patients with locally advanced esophageal squamous cell carcinoma (LAESCC). We reviewed 194 consecutive patients treated with dCRT for biopsy-confirmed LAESCC. A total of 51 patients met the inclusion criteria. Interim response was assessed by defining a region of interest in initial and adaptive computed tomography (CT) images and subsequently examined against the overall treatment response assessed three months after dCRT, treatment failure pattern, overall survival (OS), and progression-free survival (PFS) estimates. Reductions in both the area and maximal diameter of the primary lesion (p < 0.001; p < 0.001, respectively) and those of the metastatic lymph nodes (LN) (p = 0.002; p < 0.001, respectively) in interim analysis were significantly higher among patients who achieved complete response (CR) than among those who did not. OS was significantly longer among patients who showed ≥30% interim reduction in the area and maximal diameter of the primary lesion and among those who showed such reduction in both the primary lesion and LN. PFS was significantly longer in the patients with ≥30% interim reduction in the area of the primary lesion. In addition, the proportion of cases with locoregional failure began decreasing at interim response of 20% or higher, while the proportion of cases with outfield failure followed the opposite pattern, increasing at interim response of 20% or higher. Among patients treated with dCRT for LAESCC, interim response assessed using adaptive CT images correlated with overall CR and OS rates. The evaluation of tumor burden reduction during dCRT may help predict patient prognosis.
| S-EPMC8000322 | biostudies-literature
Project description:BackgroundsIn this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).MethodsPre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.ResultsFifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ?3 cm (favorable, odds ratio (OR): 4.85, P?=?0.001), patient age >55 years (favorable, OR: 1.95, P?=?0.035), and being a non-smoker (favorable, OR: 3.6, P?=?0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.ConclusionAge, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.
| S-EPMC4050419 | biostudies-literature
Project description:BackgroundWe conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n = 83) and in all sets.ResultsA high SUVmean (> 5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p < 0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9 and 92.1% in the training set, 95.8 and 97.1% in the testing set, and 92.2 and 91.8% in all sets, respectively).ConclusionsThe pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.
| S-EPMC7288413 | biostudies-literature
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses. MiRNA expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery using Agilent human miRNA microarrays based on miRBase (release 18.0) GeneChip®.
2015-07-27 | E-GEOD-59974 | biostudies-arrayexpress
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses.
2015-07-27 | GSE59974 | GEO
Project description:BackgroundMarginally resectable and unresectable soft tissue sarcomas (STS) remain a therapy challenge due to the lack of highly active treatment. The aim of the study was to identify a biomarker to predict the pathological response (PR) to preplanned treatment of these STSs.MethodsIn the phase II clinical trial (NCT03651375), locally advanced STS patients received preoperative treatment with a combination of doxorubicin-ifosfamide chemotherapy and 5 × 5 Gy radiotherapy. PR to the treatment was classified using the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group recommendations. We have chosen HIF-1α, CD163, CD68, CD34, CD105, and γH2AFX proteins, rendering different biological phenomena, for biomarker study.ResultsNineteen patients were enrolled and in four cases a good PR was reported. The high expression of HIF-1α before surgery showed a negative correlation with PR, which means a poor response to therapy. Furthermore, the samples after surgery had decreased expression of HIF-1α, which confirmed the correlation with PR. However, high expression of γH2AFX positively correlated with PR, which provides better PR. The high number of positive-staining TAMs and the high IMVD did not correlate with PR.ConclusionsHIF1α and γH2AFX could be potential biomarkers for PR prediction after neoadjuvant treatment in STS.
| S-EPMC10252106 | biostudies-literature
Project description:Neoadjuvant treatment followed by esophagectomy has been the standard strategy for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Pathological response after neoadjuvant treatment is of vital importance in the determination of long-term survival. Due to the involvement of microRNAs (miRNAs) in ESCC, some studies have proposed miRNA models to predict the pathological response. We aimed to summarize current studies on the predictive value of the miRNA models. We searched the relevant studies on PubMed, Web of Science and Cochrane Library up to February 14, 2020, using the following search term: (esophageal OR esophagus OR oesophageal OR oesophagus) AND (miR OR miRNA OR microRNA) AND (neoadjuvant OR preoperative OR induction). The initial search retrieved 206 studies. We briefly summarized the involvement of miRNAs in the origin, development and chemo- and radioresistance in ESCC. Then, 9 studies were enrolled in the systematic review. A great heterogeneity was observed across these studies. Of the 6 studies with diagnostic tests, the area under curve varied a lot. Although much evidence demonstrated the correlation between miRNAs and pathological response after in ESCC, the current studies has not established any promising models. A well-designed prospective study is essential to investigate the potential predictive models for pathological response after neoadjuvant treatment in ESCC.
| S-EPMC8033340 | biostudies-literature
Project description:ImportanceThe prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.ObjectiveTo compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC.Design, setting, and participantsThe Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.InterventionsPatients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization.Main outcomes and measuresThe primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.ResultsA total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively.Conclusions and relevanceIn this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.Trial registrationClinicalTrials.gov Identifier: NCT01216527.
| S-EPMC8223138 | biostudies-literature