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Pretreatment nutritional risk scores and performance status are prognostic factors in esophageal cancer patients treated with definitive chemoradiotherapy.

ABSTRACT: This study evaluated the prognostic effects of nutritional risk scores and performance status (PS) on unresectable locally advanced esophageal cancer (LAEC) patients who were treated with definitive concurrent chemoradiotherapy (dCRT). A total of 202 LAEC patients from four different cancer centers were retrospectively reviewed. Nutritional risk and PS were measured using the Nutritional Risk Screening 2002 (NRS-2002) scores and Eastern Cooperative Oncology Group (ECOG) scales. Outcomes were clinical response rate, overall survival (OS) and progression-free survival (PFS). Multivariate analysis of predictive factors of response to dCRT and survival were performed using a logistic regression and a Cox model, respectively. The majority of patients (71.8%) had an ECOG PS score of 0-1, and 52.5% (n=106) of patients were identified as having nutritional risk (NRS-2002 ?3) upon treatment initiation. There was no correlation between NRS-2002 scores and ECOG PS (Spearman's ?=0.046; P=0.516). In multivariate analysis, NRS-2002 scores (P=0.002, HR 2.805, 95%CI: 1.445-5.446) and ECOG PS (P=0.015, HR 2.719, 95%CI: 1.218-6.067) were independent prognostic factors for the response to dCRT. NRS-2002 scores (OS: HR 1.530, 95%CI 1.059-2.209; P=0.023; PFS: HR 1.517, 95%CI 1.105-2.082; P=0.010) and ECOG PS (OS: HR 1.729, 95%CI 1.185-2.522; P=0.005; PFS: HR 1.678, 95%CI 1.179-2.387; P=0.004) were both independent prognostic factors for OS and PFS. In conclusions, NRS-2002 scores and ECOG PS scales both have prognostic effects on clinical response and survival in LAEC, but a significant association of NRS-2002 scores and ECOG PS were not observed.

SUBMITTER: Song T

PROVIDER: S-EPMC5716782 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Role of nutritional status and intervention in oesophageal cancer treated with definitive chemoradiotherapy: outcomes from SCOPE1.

Project description:BackgroundMalnutrition is common in oesophageal cancer. We aimed to identify nutritional prognostic factors and survival outcomes associated with nutritional intervention in the SCOPE1 (Study of Chemoradiotherapy in OesoPhageal Cancer with or without Erbitux) trial.MethodsTwo hundred and fifty eight patients were randomly allocated to definitive chemoradiotherapy (dCRT) +/- cetuximab. Nutritional Risk Index (NRI) scores were calculated; NRI<100 identified patients at risk of malnutrition. Nutritional intervention included dietary advice, oral supplementation or major intervention (enteral feeding/tube placement). Univariable and multivariable analyses using Cox proportional hazard modelling were conducted.ResultsAt baseline NRI<100 strongly predicted for reduced overall survival (hazard ratio (HR) 12.45, 95% CI 5.24-29.57; P<0.001). Nutritional intervention improved survival if provided at baseline (dietary advice (HR 0.12, P=0.004), oral supplementation (HR 0.13, P<0.001) or major intervention (HR 0.13, P=0.003)), but not if provided later in the treatment course. Cetuximab patients receiving major nutritional intervention had worse outcomes compared with controls (13 vs 28 months, P=0.003).ConclusionsPre-treatment assessment and correction of malnutrition may improve survival outcomes in oesophageal cancer patients treated with dCRT. Nutritional Risk Index is a simple and objective screening tool to identify patients at risk of malnutrition.

| S-EPMC4947693 | biostudies-literature

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for patients with locally advanced esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

Project description:The present study evaluated the clinical and prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (dCRT). A total of 517 patients with ESCC were enrolled and analysed retrospectively. The NLR was calculated at three time points: baseline, post-treatment, and at the time of tumor progression. Elevated NLR was defined as a ratio ≥5. High NLR at baseline was present in 204 (39%) patients and was significantly correlated with larger tumour size, advanced TNM stage, worse ECOG performance status, and dCRT response (p < 0.05). At a median follow-up of 17 months, patients with higher NLR at baseline had poorer progression-free survival (PFS) and overall survival (OS). On multivariate analysis, elevated NLR at baseline was independently associated with PFS and OS (HR = 1.529, p < 0.001 for PFS; HR = 1.856, p < 0.001 for OS). In addition, patients with high pre- and post-treatment NLR demonstrated worse clinical outcomes than other groups. Our results suggest that NLR is an independent prognostic indicator for patients with ESCC undergoing dCRT and changes in NLR level with treatment may indicate therapeutic benefit.

| S-EPMC5307338 | biostudies-literature

YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma.

Project description:BackgroundDefinitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment.MethodsTo identify prognostic biomarkers, we performed targeted next-generation sequencing of 416 cancer-related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) was analyzed.ResultsTP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08-0.77, P = .015) and progression-free survival (PFS) (HR, 0.35; 95%CI, 0.13-0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26-13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95-8.17, P = .062). In a subgroup analysis, while sex and M-stage were controlled, a much stronger negative effect of YAP1 amplification vs wild-type in LRFS was observed (log-rank P = .0067).ConclusionThe results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored.

| S-EPMC7050074 | biostudies-literature

Prognostic Significance of Interim Response Evaluation during Definitive Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

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

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

Project description:Background and purposeThe derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial.Materials and methods258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS).ResultsAn elevated pre-treatment dNLR?2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR?2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours.ConclusionsAn elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].

| S-EPMC5648078 | biostudies-literature

Risk factors for esophageal fistula in thoracic esophageal squamous cell carcinoma invading adjacent organs treated with definitive chemoradiotherapy: a monocentric case-control study.

Project description:BACKGROUND:Standard treatment for unresectable esophageal squamous cell carcinoma (ESCC) without distant metastasis is definitive chemoradiotherapy (dCRT), in which the incidence of esophageal fistula (EF) is reported to be 10-12%. An ad hoc analysis of JCOG0303, a phase II/III trial of dCRT for patients with unresectable ESCC (including non-T4b), suggested that esophageal stenosis is a risk factor for EF. However, risk factors for EF in patients limited to T4b ESCC treated with dCRT have yet to be clarified. The aim of this study was to investigate risk factors for EF in T4b thoracic ESCC treated with dCRT. METHODS:We retrospectively analyzed the data of consecutive T4b thoracic ESCC patients who were treated with dCRT (cisplatin and fluorouracil) at Shizuoka Cancer Center between April 2004 and September 2015. RESULTS:Excluding 8 patients with esophageal fistula clearly attributable to other iatrogenic interventions, the data of 116 patients who met the inclusion criteria were analyzed. Esophageal fistula was observed in 28 patients (24%). Although the fistula was closed in 5 patients, overall survival was significantly shorter in patients who experienced esophageal fistula (8.0 vs. 26.8 months; p?<?0.0001). Among four potential variables extracted in univariate analysis, namely, total circumferential lesion, elevated CRP level, elevated white blood cell count, and anemia, the first two were revealed as risk factors for esophageal fistula in multivariate analysis. CONCLUSIONS:This study demonstrated that total circumferential lesion and CRP ?1.00 mg/dL are risk factors for esophageal fistula in T4b thoracic ESCC treated with dCRT. TRIAL REGISTRATION:This study was retrospectively registered.

| S-EPMC5960135 | biostudies-literature

Optimal radiotherapy dose in cervical esophageal squamous cell carcinoma patients treated with definitive concurrent chemoradiotherapy: A population based study.

Project description:BackgroundThe optimal radiotherapy dose for locally advanced cervical esophageal squamous cell carcinoma (C-ESqCC) treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. Here, we aimed to compare the survival of those treated with high dose versus standard dose via a population based approach.MethodsEligible C-ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between high (60-70 Gy) and standard dose (50-50.4 Gy). We also evaluated the outcome in supplementary analyses via alternative approaches.ResultsOur primary analysis consisted of 141 patients in whom covariates were well balanced after PS weighting. The HR of death when high dose was compared with standard dose was 0.65 (95% confidence interval [CI]: 0.4-1.03, p = 0.07). The HR of IECM was 0.74 (p = 0.45). The HR of OS remained similarly insignificant in supplementary analyses.ConclusionsWe observed a trend in favor of high radiotherapy dose versus standard dose for C-ESqCC treated with dCCRT in this population-based nonrandomized study. Further studies are needed to confirm the findings of the study.

| S-EPMC8287021 | biostudies-literature

Definitive chemoradiotherapy.

Project description:Definitive chemoradiotherapy (dCRT) is reflecting a treatment standard in oesophageal cancer. For irresectable localised tumours and for inoperable patients, dCRT can change the treatment intent from palliative to curative. In patients with squamous cell carcinoma (SCC), in particular in those of cervical location, dCRT is a proper alternative for treatment that may include radical surgery. Patients with localised locoregional recurrence after primary surgery can survive for long-term after salvage CRT.

| S-EPMC5538992 | biostudies-other

Prognostic significance of lung radiation dose in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy.

Project description:BACKGROUND:The prognostic significance of radiation dose to the lung or heart is unknown in esophageal cancer patients receiving neoadjuvant chemoradiotherapy followed by surgery (trimodal therapy). This study aimed to determine the association between lung and heart radiation dose volumes and prognosis of esophageal cancer after trimodal therapy. METHODS:This study reviewed 123 esophageal cancer patients treated with trimodal therapy in two tertiary institutions between 2010 and 2015. The dose-volume histogram parameter of Vx was defined as the percentage of total organ volume receiving a radiation dose of x (Gy) or more. Predictors of overall survival (OS) were identified using Cox regression models. Receiver-operating characteristic curves were used to select cut-off values for dose-volume. RESULTS:Median follow-up was 28.3 months (range: 4.7-92.8 months). Median OS and progression-free survival were 34.0 months (95% confidence interval [CI]: 27.4-40.6 months) and 24.8 months (95% CI, 18.9-30.7 months), respectively. Multivariate analyses showed that lung V20 (hazard ratio, 1.09; 95% CI: 1.04-1.14; p < 0.001) and lung V5 (hazard ratio, 1.02; 95% CI: 1.00-1.05; p = 0.03) were associated with OS when adjusting for surgical margin and pathological treatment response. The 5-year OS for patients with lung V20 ≤ 23% vs. patients with lung V20 > 23% was 54.4% vs. 5% (p < 0.001) whereas that for patients with lung V5 ≤ 56% vs. patients with lung V5 > 56% was 81.5% vs. 23.4% (p < 0.001). Mean heart dose showed no association with survival outcomes. CONCLUSIONS:Lung radiation dose was independently associated with survival outcomes in esophageal cancer patients treated with neoadjuvant chemoradiotherapy and surgery.

| S-EPMC6534831 | biostudies-other

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery for stage II to III esophageal squamous cell carcinoma.

Project description:OBJECTIVE:Definitive chemoradiotherapy (CRT) remains the most commonly used treatment for locally advanced esophageal squamous cell carcinoma (SCC), because of perceptions that esophagectomy offers an unclear survival advantage. We compare recurrence, overall survival (OS), and disease-free survival (DFS) in patients treated with definitive CRT or neoadjuvant CRT followed by surgery (trimodality). METHODS:This was a retrospective cohort study of patients with stage II and III SCC of the middle and distal esophagus in patients who completed CRT. Treatment groups were matched (1:1) on covariates using a propensity score-matching approach. The effect of trimodality treatment, compared with definitive CRT, on OS, DFS, and site-specific recurrence was evaluated as a time-dependent variable and analyzed using Cox regression with a gamma frailty term for matched units. RESULTS:We included 232 patients treated between 2000 and 2016: 124 (53%) with definitive CRT and 108 (47%) with trimodality. Trimodality was used less frequently over time (61% before 2009 and 29% after 2009; P < .0001). After matching, each group contained 56 patients. Median OS and DFS were 3.1 and 1.8 years for trimodality versus 2.3 and 1.0 years for CRT. Surgery was independently associated with improved OS (hazard ratio, 0.57; 95% confidence interval, 0.34-0.97; P = .039) and DFS (hazard ratio, 0.51; 95% confidence interval, 0.32-0.83; P = .007). CONCLUSIONS:CRT followed by surgery might decrease local recurrence and increase DFS and OS in patients with esophageal SCC. Until better tools to select patients with pathological complete response are available, surgery should remain an integral component of the treatment of locally advanced esophageal SCC.

| S-EPMC5960990 | biostudies-literature

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