Chemoradiotherapy For Esophageal Carcinoma Research Articles

Factors influencing decision-making between surgery and chemoradiotherapy for esophageal carcinoma from the JCOG0502.

Aim: Treatment options for esophageal squamous cell carcinoma includes surgery and chemoradiotherapy (CRT), however there was limited information about the factors influenced in patients' decision-making.Materials & methods: Patients who participated in JCOG0502, a parallel group controlled trial comparing surgery with CRT, were analyzed for the factors related to decision-making.Results: Of the 368 patients (pts) enrolled in the nonrandomized part in JCOG0502, 209 pts opted for surgery and 159 pts chose CRT on their own. Background characteristics were the same except for age. Multivariable logistic regression analysis showed that age ≥65years, male sex, multiple lesions, absence of children and doctor's thinking were associated with the selection of CRT.Conclusion: The doctor's option was the most influential factor in the patient's decision-making process.Clinical Trial Registration: UMIN000000551 (ClinicalTrials.gov).

Neoadjuvant chemoradiotherapy plus tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): the protocol of a prospective, single-arm, phase II trial

BackgroundThe failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%–48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown.MethodsPatients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II–IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab.DiscussionThe optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma.Trial registrationThis study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov (NCT04776590) on March 1, 2021.

MO43-3 Prognostic value of systemic inflammation score in patients treated with chemoradiotherapy for esophageal carcinoma

Systemic inflammation score (SIS) is one of the prognostic indicators using lymphocyte-to-monocyte ratio (LMR) and serum Alb level, and has been reported in various solid tumors recently. However, its significance in patients treated with chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study is to investigate the clinical usefulness of SIS in patients who underwent CRT for ESCC.

Clinical response to chemoradiotherapy in esophageal carcinoma is associated with survival and benefit of consolidation chemotherapy.

PurposeFew studies have reported the impact of the clinical response of patients with Esophageal Carcinoma to chemoradiotherapy (CRT). Our study examines the association between clinical response and pretreatment variables, survival, patterns of failure, and benefit of consolidation chemotherapy in subjects with esophageal squamous cell carcinoma (ESCC) patients receiving CRT.MethodsData from ESCC patients treated at Shandong Cancer Hospital between January 2013 and December 2016 were analyzed retrospectively. By definition, we considered a poor response as progressive disease (PD) and stable disease (SD), while complete response (CR) and partial response (PR) were considered as a good response. Multivariate analyses were carried out using Cox proportional hazards models and patient survival was assessed using the Kaplan‐Meier and log‐rank test.ResultsAfter CRT, 136 (48.9%) patients responded well (good response) and 152 (51.1%) patients responded poorly (poor response). Overall survival (OS) and progression‐free survival (PFS) differed significantly between patients responded well and those responded poorly. Patients with an early‐stage or the upper location of the tumor were more likely to achieve a good response. Patients showing poor responses tended to experience local failure. The 3‐year OS and PFS rates of patients showing poor response were 38.9% and 25.5%, respectively, for the CRT with consolidation chemotherapy (CRT + C) group, and 22.7% and 16.7%, respectively, for the CRT group. However, patients with a good response did not benefit from the consolidation chemotherapy. Primary tumor location, T category, N category, and clinical response to chemoradiotherapy were independent factors predicting OS and PFS in ESCC.ConclusionClinical response to CRT substantially improves patient survival and is associated with failure patterns in ESCC. Consolidated chemotherapy may benefit patients with a poor response.

Combination of DCE-MRI and DWI in Predicting the Treatment Effect of Concurrent Chemoradiotherapy in Esophageal Carcinoma.

Background Concurrent chemoradiotherapy (CCRT) is the main treatment for esophageal cancer, but the response to treatment varies from individual to individual. MR imaging methods, such as diffusion-weighted (DW) MRI and the use of dynamic contrast-enhanced (DCE) MRI, have the potential to provide additional biomarkers that could evaluate the effect of CCRT in patients with esophageal carcinoma. Materials and Methods Fifty-six patients with esophageal carcinoma, verified by histopathology, underwent MRI examination before and at midtreatment (4th week, radiotherapy 30–40 Gy) using the Siemens 3.0 T MR System. Parameter maps of apparent diffusion coefficient (ADC), and DCE maps of volume transfer constant (Krans), rate contrast (kep), and extracellular fluid space (ve), were computed using a Siemens Company Multimodality Workplace (MMWP) model. Comparison of histogram parameters and their diagnostic performance was determined using the Mann–Whitney U test and receiver operating characteristic (ROC) analysis. Results 56 patient MRI scans were available for analysis at baseline and at the third week, respectively. Pretreatment Krans, pretreatment kep, pretreatment ADC (P < 0.05), and during-treatment Krans (P < 0.05) and ΔKrans and ΔADC (P < 0.05) were significantly different after CCRT. Based on the binary logistic model, the ROC analysis demonstrated that the combined predictors demonstrated a high diagnostic performance with an AUC of 0.939. The sensitivity and specificity were 98.6% and 73.8%, respectively. Conclusion The combination of DCE and DWI can be used as an early biomarker in the prediction of the effect of CCRT three weeks after treatment in esophageal carcinoma.

ADC correlation with Sirtuin1 to assess early chemoradiotherapy response of locally advanced esophageal carcinoma patients

AimsTo determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT).MethodsA total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1~2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and ΔADC, ADCratio were calculated. Pearson’s correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman’s rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT.ResultsThe findings of this study showed different correlations between ADC values and the levels of SIRT1 (ΔADC: r = − 0.943, P = 0.002; ADCratio: r = − 0.911, P = 0.000; intra-ADC: r = − 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between ΔADC and early response to treatment (ρ = 0.615, P = 0.023), and multivariable logistic regression revealed that ΔADC was significantly associated with short-term response of CRT in esophageal carcinoma patients.ConclusionsIn summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.

Pathological response and serum VEGF changes during chemoradiotherapy for esophageal carcinoma.

The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (P < .001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (P < .05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (P < .05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (P < .05). Pathological response (P < .05), serum VEGF trend (P < .05), and tumor-node-metastasis stage (P < .05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.

EP-1413: Clinical efficacy between single and dual-agent chemoradiotherapy in esophageal carcinoma

EP-1413: Clinical efficacy between single and dual-agent chemoradiotherapy in esophageal carcinoma

Radiotherapy for esophageal carcinoma: dose, response and survival.

Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor) after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients.

Radiomic analysis in contrast-enhanced CT: predict treatment response to chemoradiotherapy in esophageal carcinoma.

ObjectivesTo investigate the capability of computed-tomography (CT) radiomic features to predict the therapeutic response of Esophageal Carcinoma (EC) to chemoradiotherapy (CRT).MethodsPretreatment contrast-enhanced CT images of 49 EC patients (33 responders, 16 nonresponders) who received with CRT were retrospectively analyzed. The region of tumor was contoured by two radiologists. A total of 214 features were extracted from the tumor region. Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to evaluate the capability of each feature on treatment response classification. Support vector machine (SVM) and artificial neural network (ANN) algorithms were used to build models for prediction of the treatment response. The statistical difference between the performances of the models was assessed using McNemar’s test.ResultsRadiomic-based classification showed significance in differentiating responders from nonresponders. Five features were found to discriminate nonresponders from responders (AUCs from 0.686 to 0.727). Considering these features, two features (Histogram2D_skewness: P = 0.015. Histogram2D_kurtosis: P = 0.039) were significant for differentiating SDs (stable disease) from PRs (partial response) and one feature (Histogram2D_skewness: P = 0.027) for differentiating SDs from CRs (complete response). Both classifiers showed potential in predicting the treatment response with higher accuracy (ANN: 0.972, SVM: 0.891). No statistically significant difference was observed in the performance of the two classifiers (P = 0.250).ConclusionsCT-based radiomic features can be used as imaging biomarkers to predict tumor response to CRT in EC patients.

Nutrition Status and Inflammatory Indexes Could Predict Acute Toxicity After Concurrent Chemoradiation Therapy for Esophageal Carcinoma

To evaluate the influence on acute toxicity with different nutrition status and inflammatory indexes ofthe patients after concurrent chemoradiotherapy in esophageal carcinoma. A total of 338 cases of esophageal carcinoma who underwent intensity modulated radiation therapy (IMRT)with concurrent chemotherapy were eligible for retrospectively analysis. The influence on acute toxicity with different nutrition status such as body mass index level (BMI), albumin level (ALB), total lymphocyte count level (TLC), anemia and inflammatory indexes including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were observed after the treatment. The incidence rate of malnutrition according to different nutrition status was ranging from 5.62% to 54.14%. The incidence of acute radiation esophagitis of grade 2 and above in low ALB group were higher than that in normal ALB group (χ2=75.677，P=0.000). The incidence of hematologic toxicity among different TLC levels had statistical difference significantly. With the decline of TLC level, the incidence of hematologic system toxicity was increased (χ2=12.891，P=0.006), but the rate of acute radiation pneumonitis was decreased (χ2=19.775，P=0.001). The incidences of acute radiation esophagitis of grade 2 and above in anemia group were much higher than that in normal group (χ2=37.774, P=0.000). An higher incidence of acute radiation esophagitis was shown in NLR and PLR high level groups than in lower NLR and PLR groups (χ2=64.207, P=0.000; χ2=11.260, P=0.004). Accompanied by NLR and PLR levels elevate,the rate of acute radiation esophagitis is ascendant, where as the rate is decendant with ALB and Hb levels decline. The occurrence of hematologic system toxicity will increases and acute radiation pneumonitis decreases when TLC levels goes down.

Effect of nutritional status and inflammatory markers on acute adverse reactions during concurrent chemoradiotherapy for esophageal carcinoma

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed. The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined. Data were analyzed using the chi-square test with continuity correction and logistic regression analysis. Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%. The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000). The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001). In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group. Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively). Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011, respectively). Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment. In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment. Key words: Esophageal neoplasms/radiotherapy; Nutritional status; Inflammation

A clinical study of diffusion-weighted magnetic resonance imaging-based prediction of efficacy of chemoradiotherapy for esophageal carcinoma

Objective To investigate the parameters of diffusion-weighted magnetic resonance imaging (DWMRI) for prediction of the efficacy of chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC), to determine the optimal time point and threshold for prediction, and to provide a basis for clinical practice. Methods From 2010 to 2011, 38 patients with ESCC were consecutively enrolled as subjects. All patients received three-dimensional conformal radiotherapy with 60 Gy in 30 fractions for 6 weeks. They also received concurrent or consolidation chemotherapy (FP or TP scheme) as adjuvant treatment. Patients received DWMRI scans before radiotherapy and at weeks 1-6 during radiotherapy. The apparent diffusion coefficient (ADC) values and tumor lengths obtained from serial DWMRI scans were recorded and analyzed. Comparison was made by paired t test. Repeated measurements were analyzed by analysis of variance (ANOVA) and multivariate ANOVA. The prognosis was predicted by the Logistic model. The effectiveness analysis and threshold screening were performed using the receiver operating characteristic (ROC) curve. Results In all patients, 20(52.6%) had complete response (CR) and 18(47.4%) had partial response (PR). There were no significant differences in the ADC values before radiotherapy and at weeks 1-6 during radiotherapy between patients with CR and PR (1.82 vs. 1.42; 1.92 vs. 1.49; 2.06 vs. 1.67; 2.35 vs. 1.79; 2.62 vs. 2.11; 2.71 vs. 2.18; 2.96 vs. 2.28×10-3 mm2/s; P=0.006, 0.003, 0.012, 0.001, 0.003, 0.008, 0.002). The ADC value at third week during radiotherapy was the only independent prognostic factor for short-term treatment outcomes in patients with ESCC (OR=0.134, P=0.007). These results were also supported by the multivariate ANOVA analyses. The analysis of the ROC curve showed that at the third week during radiotherapy, the area under the ADC curve was the largest (Az=0.857) and the diagnostic effectiveness was the best; the threshold value, sensitivity, and specificity were 2.02×10-3 mm2/s, 80.0%, and 92.9%, respectively. Eight patients who had tumor out of control or recurrence within 1 year after treatment had the ADC curve fall down at the end of the fifth week and the reduction of tumor length substantially slow down from the fifth week. Conclusions DWMRI is an effective imaging approach for monitoring tumor response to CRT in patients with ESCC. The ADC value at the end of the third week during radiotherapy may be the optimal time point for prediction of treatment outcomes. The reduction in the ADC value or non-reduction in tumor length at the end of the treatment indicates a high risk of recurrence. Key words: Diffusion-weighted magnetic resonance imaging; Apparent diffusion coefficient; Predic therapeutic effect; Esophageal neoplasms/radiotherapy

2270 Patterns of relapse following definitive chemoradiotherapy for oesophageal carcinoma - is there a case for elective nodal irradiation?

2270 Patterns of relapse following definitive chemoradiotherapy for oesophageal carcinoma - is there a case for elective nodal irradiation?

The prognostic value of a modified tumor regression grade after neoadjuvant chemoradiotherapy and resection of esophageal carcinoma.

4066 Background: The tumor regression grade (TRG) is used to define the response to preoperative chemoradiotherapy for esophageal carcinoma. The aim of this study was to determine whether inclusion...

PET/CT-based metabolic tumour volume for response prediction of neoadjuvant chemoradiotherapy in oesophageal carcinoma

Neoadjuvant chemoradiotherapy is increasingly used in oesophageal cancer patients. In general, small tumours are associated with a survival benefit compared to large tumours. Little is known, however, about the relationship between initial tumour volume and response to chemoradiotherapy. Therefore, the aim of this study was to determine whether the pretherapy metabolic tumour volume (MTV) on diagnostic PET/CT in oesophageal cancer patients is correlated with response to chemoradiotherapy in the resection specimen. A consecutive series of patients underwent diagnostic PET/CT scanning prior to chemoradiotherapy and oesophagectomy. MTVs were determined on PET/CT and an automated tumour contour was generated using specified standard uptake value thresholds. Response to chemoradiotherapy was determined in the resection specimen according to the scoring system developed by Mandard et al. Patients were divided into different groups according to response to chemoradiotherapy. Between January 2008 and May 2011 a total of 115 patients underwent an oesophagectomy. The MTV determined on diagnostic PET/CT scans was available in 79 patients. Of these 79 patients, 30 (38 %) showed no residual tumour cells at the location of the primary tumour. Three of these patients presented with residual tumour cells in the lymph nodes; 27 patients (34 %) had a complete pathological response. There was a trend towards a better response in patients with a smaller MTV (p = 0.084). This study demonstrated a trend towards a correlation between response to chemoradiotherapy in oesophageal cancer patients and smaller MTVs as determined on diagnostic PET/CT prior to neoadjuvant chemoradiotherapy. However, tumour volumes overlapped between groups, indicating the need for multifactorial parameters as predictors. In addition, a complete local tumour response may be accompanied by residual disease in the regional lymph nodes.

Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma.

Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m(2) ) or nonobese (BMI < 25 kg/m(2) ). Progression-free survival and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis-free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy- and radiotherapy-related treatment toxicities.

Abstract 2429: Airway necrosis after salvage esophagectomy.

Abstract Background: Recently definitive chemoradiotherapy (CRT) without surgery has been accepted as an alternative treatment for esophageal cancer. However, unfortunately, the tumors of 5-33% patients were resistant to CRT and persistent disease was detected soon after treatment, and 16-54% patients initially showed a response but locoregional disease was discovered later. Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive CRT for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Methods: Between 1997 and 2007, 49 patients with thoracic esophageal squamous cell carcinoma underwent salvage esophagectomy after definitive CRT. All patients received more than 50 Gy of radiation plus concurrent chemotherapy for curative intent. We retrospectively compared patients with and without airway necrosis. Additionally, airway necrosis was categorized primary necrosis and secondary necrosis according to the cause of necrosis, and operative procedures related to airway necrosis were investigated. Result: Overall 23of 49 patients had at least one complication (morbidity: 46.9%), and 5 died during their hospitalization (mortality: 10.2%). Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery (BA), cervical and subcarinal lymph node dissection (LND) and reconstruction route. Primary necrosis occurred in 3 patients with resection of BA, cervical LND, or subcarinal LND. And bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Conclusions: Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. Citation Format: Norimitsu Tanaka, Nobukazu Hokamura, Yuji Tachimori. Airway necrosis after salvage esophagectomy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2429. doi:10.1158/1538-7445.AM2013-2429

Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy

BackgroundP53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma.MethodsSerum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted.ResultsTwenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT.ConclusionsAnti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.

Cardiac toxicity associated with dose and gender in patients undergoing chemoradiation for esophageal carcinoma.

112 Background: The purpose of this study was to identify factors associated with symptomatic cardiac toxicity in patients treated with chemoradiotherapy (CRT) for esophageal carcinoma. Methods: One-hundred and forty-four patients with adenocarcinoma or squamous cell carcinoma were treated from 7/2002 - 6/2011 at 2 academic institutions with pre-operative, definitive or palliative CRT. Chemotherapy and radiation therapy was administered at the discretion of the treating oncologist. Altogether, 120 patients had sufficient dose volume histogram (DVH) data for analysis and ≥3 month follow up from treatment completion. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass/angioplasty, diabetes, insulin use, smoking, and tumor location (upper/middle vs. lower/GE junction). T-test assessed risk of cardiac toxicity secondary to age. Percentage of heart volume receiving &gt;20, 30, 40, and 50 Gy (V20-V50) and its association with cardiac toxicity was evaluated for each patient. Fisher’s exact test was used to test for an association between dose volume parameters and cardiac toxicity. Results: Patient population included 93 males and 27 females with a mean age of 63 years. Any cardiac toxicity occurred in 27 patients, 8 of which were symptomatic. T-test comparing age to toxicity was not significant; however, female patients were 3.57 times more likely to have cardiac toxicity ([95% Confidence Interval 1.42-9.01], p=0.005). A significant difference in V40 existed between patients with cardiac toxicity and those without (p=0.05). Patients above the median cut-off for V40 (54%) had 2.48 increased odds of developing cardiac toxicity ([95% Confidence Interval 1.02-6.02], p=0.04). None of the other investigated variables were associated with an increased risk of developing cardiac toxicity. Conclusions: Female patients were found to have an increased risk of cardiac toxicity subsequent to receiving CRT for esophageal carcinoma. V40 greater than 54% was associated with increased cardiac toxicity. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma.