Radiotherapy For Esophageal Cancer Research Articles

Prediction of radiation pneumonia after radiotherapy for esophageal cancer using a unified fractional dosiomics combined model.

This study aimed to construct an optimal model to predict radiation pneumonia (RP) after radiotherapy for esophageal cancer using unified fractional dosiomics and to investigate the improvements in the prediction efficiency of each model for RP. The clinical data, DVH, pre-treatment CT, and dose distribution of 182 patients were retrospectively analyzed.The independent risk factors were screened using univariate and multivariate logistic regression. The mutual information (MI),least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE) methods were used to screen the omics features. The AUC values of ROC, calibration curves, and clinical decision curves were calculated to evaluate the efficacy and trends of each model. The AUC of dosiomics model were 0.783 and 0.760 in the training and test cohorts, higher than 0.585 and 0.579 in the training and test cohorts of the DVH model. The AUC value of the R + D combination was the highest, reaching 0.833. The combined R + D model had a better calibration degree than the other models (mean absolute error = 0.018) and better net benefit in clinical decision-making. The radiomics combined dosiomics model was the best combined model to predict RP after radiotherapy for esophageal cancer. The dosiomics model could cover the efficiency of the DVH model and significantly improve the efficiency of the combined model.In the future, we will include other centers for further verification. For the first time, this study used CT images combined dose distribution to predict the occurrence of radiation pneumonitis after radiotherapy for esophageal cancer.

Radiotherapy for Advanced Esophageal Cancer: from Palliation to Curation.

Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.

Study on the Dynamic Changes of Myocardial Injury Markers in Radiotherapy for Esophageal Carcinoma and Its Correlation with Cardiac Dosimetry

It was hypothesized that radiotherapy for esophageal cancer could cause radiation-induced heart damage. To investigate the dynamic changes of myocardial enzyme, high-sensitive troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide precursors (PRO-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy and six months after radiotherapy for middle and lower thoracic squamous cell carcinoma, and to analyze the correlation between these indicators and dose-volume histogram (DVH) parameters of the heart. A total of 35 patients with thoracic esophageal squamous cell carcinoma who underwent radical concurrent chemoradiotherapy were enrolled in the study. Radiation therapy was performed for up to 6 weeks. All patients received Intensity modulated radiation therapy (IMRT). Total radiation dose was from 50.4Gy to 60 Gy in each patient with a dose of 1.8-2.0 Gy per fraction. Blood samples to determine creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactic dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBDH), hs-TnT, PRO-BNP and LVEF were measured before radiotherapy, during (10th -20th fraction), at the end of radiotherapy, 1, 3, 6 months after radiotherapy. The dynamic changes of the above indexes were analyzed. The correlation between the above indexes and the mean heart dose (Dmean), V5-V60 (dose-volume histograms data were recorded in discrete 5Gy dose levels) of the heart in the course of radiotherapy was also analyzed. The Serum hs-TNT and LVEF show an upward trend during radiotherapy, at the end of radiotherapy and 6 months after radiotherapy for esophageal cancer. The hs-TnT of patients before, during, at the end of radiotherapy and 1, 3, and 6 months after radiotherapy were 7.2pg/ml, 9.1pg/ml, 9.1pg/ml, 9.0pg/ml, 9.4pg/ml, and 8.1pg/ml, respectively (p<0.05). The LVEF were 63.7%, 62.4%, 62.0%, 62.5%, 62.2%, 61.9% respectively (p<0.05). The pro-BNP showed an upward trend during radiotherapy and gradually returned to normal after radiotherapy. The CK and CK-MB showed a downward trend during radiotherapy and 1 month after radiotherapy, and gradually returned to normal 3 months after radiotherapy. Compared with the low dose group (the average dose of heart < 2000cGy), the high dose group (≥2000cGy) had a greater increase in hs-TNT, pro-BNP and LVEF, and a slower recovery time. There was no correlation between the changes of myocardial enzyme, hs-TnT, PRO-BNP, LVEF and the heart mean dose, V5-V60 during radiotherapy (p>0.05). Cardiac injury induced by concurrent chemoradiotherapy for middle and lower thoracic esophageal cancer can lead to the increase of serum hs-TNT and pro-BNP and the increase of LVEF in the early stage of treatment, and this phenomenon is more obvious in the high-dose group. The hs-TnT and PRO-BNP are sensitive parameters to reflect the heart damage in esophageal cancer radiotherapy, which may provide reference for the heart protection during radiotherapy.

Enhanced Radiosensitivity of Esophagus Cancer through Loss of ADAR1 and Cell Apoptosis via NF-kB Signaling Pathway

RNA editing is a common posttranslational mechanism for generating genomic diversity by modifying selected RNA sequences without altering the genome. A new understanding of cancer therapy can be enhanced by the discovery of ADAR1 in the control of signal transduction pathways. However, the study of the biological effects of ADAR1 in radioresistance of esophageal cancer is not very deep. The TCGA data sets were used to explore the correlations between ADAR1 and prognosis in esophageal cancer. Two pairs of ADAR1 gene siRNA fragments (siADAR1-1 and siADAR1-2) were designed and transiently transfected into KYSE410 cells and KYSE410-RT cells. The expression of ADAR1 was detected by RT-PCR and WB. Colony formation assay was used to evaluate the radiosensitivity. Apoptosis was measured using a flow cytometric apoptosis assay. Furthermore, transcriptome sequencing was performed to elucidate the pathways regulated by ADAR1. In this study, we found that ADAR1 is overexpressed in esophageal tumors and is associated with poor prognosis in bioinformatics analysis. Colony formation experiment showed that siRNA-mediated depletion of ADAR1 in KYSE410 cells could inhibit cell proliferation and reduce radiosensitivity significantly. Consistently results were showed in KYSE410-RT cells. Mechanism studies revealed loss of ADAR1 induced cell apoptosis and radiotherapy could enhance this process. Transcriptomic data indicated that ADAR1 could regulate apoptosis through the NF-kB pathway. RNA editing was found to be involved in the regulation of radiosensitivity of esophageal cancer and loss of ADAR1 can cause cell apoptosis though NF-kB pathway. A better understanding of A-to-I RNA editing and its oncogenic mechanisms may facilitate the development of radiotherapy in esophageal cancer.

Electrocardiogram with Artificial Intelligence Assessment as a Predictor of Cardiac Events and Overall Survival in Patients Receiving Radiotherapy for Esophageal Cancer

Neoadjuvant (chemo)radiotherapy (RT) has demonstrated an overall survival (OS) benefit in esophageal cancer and constitutes part of the standard of care trimodality therapy. Unfortunately, subsequent cardiac toxicity can reduce the benefit of treatment. Our group aimed to study whether data from electrocardiograms (ECGs) could predict clinical outcomes and cardiac events after RT for esophageal cancer, allowing for identification of and early intervention for patients at high risk for cardiac toxicity. Included patients received at least 41.4 Gy of pre-operative or definitive photon or proton RT for esophageal cancer from 2015 through July 2022. All ECGs were assessed using a previously validated artificial intelligence assessment for atrial fibrillation (AF) and reduced ejection fraction (rEF) (Noseworthy et al. Lancet 2022). The model determined propensities for the development of multiple cardiac events, including AF and heart failure (HF). Medical records were reviewed for cardiac events and conditions prior to and after RT. A cohort of 491 patients was assembled, with 301, 121, and 364 patients having an ECG prior to, during, and after RT, respectively. Of these, 84% had malignancy in the lower third of the esophagus and 48% underwent esophagectomy. At last follow-up relative to baseline assessment, patients had increased propensity for rEF (median 0.013, interquartile range (IQR): 0.001-0.038 vs. median 0.022, IQR: 0.011-0.074, p < 0.0001) and AF (median 0.16, IQR: 0.04-0.40 vs. median 0.048, IQR: 0.01-0.19, p < 0.0001). Increases in AF propensity were associated with reduced OS (hazard ratio (HR) = 1.10 per 0.1 increase, 95% confidence interval (CI): 1.03-1.17, p = 0.0071). Baseline rEF propensity was predictive of future HF events (HR = 1.14, 95% CI: 1.07-1.22, p < 0.001) for all patients or after excluding the 172 (35%) patients with baseline HF (HR = 1.45, 95% CI: 1.19-1.76, p < 0.001). Among patients who did not have HF prior to radiotherapy, the development of HF was associated with reduced OS (HR = 1.60, 95% CI: 1.10-2.32, p = 0.014). Currently available cardiac dosimetric parameters, including heart mean/max doses, did not significantly correlate with cardiac outcomes. Patients who underwent esophagectomy had improved OS (HR = 0.62, 95% CI: 0.47-0.82, p = 0.0008) and were not more likely to develop cardiac toxicity. This analysis suggests that chemoradiotherapy for esophageal cancer can have significant impacts on a patient's propensity for cardiac events, which are associated with reduced OS. ECGs carry the potential to identify patients at greater risk for such events, and baseline ECGs with artificial intelligence assessment could select patients for increased surveillance or early intervention to further optimize the therapeutic ratio of RT.

Retracted: Serum MMP-9 and SAA in the Diagnosis of Severe Pneumonia Caused by Radiotherapy of Esophageal Cancer.

[This retracts the article DOI: 10.1155/2021/6032546.].

Retracted: Risk Factors of Acute Radiation-Induced Lung Injury Induced by Radiotherapy for Esophageal Cancer.

[This retracts the article DOI: 10.1155/2022/2416196.].

Lymph node ratio evaluation precisely predicts the benefit of postoperative radiotherapy in esophageal cancer: A retrospective cohort study.

The matter of postoperative radiotherapy (PORT) in esophageal cancer (ESCA) was far from conclusive. Some evidence indicated that lymph node status could affect treatment. We evaluated lymph node ratio (LNR) as an indicator that could be applied to predict PORT benefit. Retrospective cohort study collected the data of N1, N2, N3 stage ESCA patients from the Surveillance, Epidemiology, and End Results database (SEER) to analyze the association between LNR and prognosis from 2004 to 2015. Patients were categorized into two subsets based on the LNR cut-off value of 0.23 using receiver operating characteristic curve (ROC). Kaplan-Meier analysis was utilized to estimate the proportion of overall survival (OS) and esophagus cancer-specific survival (CSS) in two LNR groups. Cox regression analysis and competitive risk model was adopted to investigate the impacts of LNR on prognosis. Of 2,165 ESCA patients identified, 1,165 (53.8%) had LNR>0.23. The LNR was an independent prognostic factor and associated with better OS and CSS of LNR≤0.23 (P<0.001). In competitive risk model, a worse CSS was analyzed of LNR>0.23 (HR=1.71; 95% CI 1.53-1.91). Subgroup analyses indicated that PORT was associated with favorable OS and CSS. Furthermore, when stratified by Node stage, PORT was associated with a survival benefit only in N1 stage with higher LNR (LNR>0.23) after adjusting for other covariates. LNR exceeding 0.23 was negatively associated with prognosis in ESCA. The survival benefit from PORT in ESCA seems to be limited to LNR of 23% or more only in N1 stage. This study highlights the biomarker meaning of LNR on identifying PORT beneficiary in N1 stage.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer

AbstractBackgroundPatients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision‐making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer.MethodsA retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5‐ and 10‐year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C‐index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan‐Meier (K‐M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five‐ and ten‐year survival rates for the two groups were shown using K‐M curves.ResultsThe major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C‐indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5‐ and 10‐year risk of cardiac death. The model exhibited moderate predictive power for 5‐ and 10‐year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively).ConclusionsOur nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Nanodrugs systems for therapy and diagnosis of esophageal cancer.

With the increasing incidence of esophageal cancer, its diagnosis and treatment have become one of the key issues in medical research today. However, the current diagnostic and treatment methods face many unresolved issues, such as low accuracy of early diagnosis, painful treatment process for patients, and high recurrence rate after recovery. Therefore, new methods for the diagnosis and treatment of esophageal cancer need to be further explored, and the rapid development of nanomaterials has brought new ideas for solving this problem. Nanomaterials used as drugs or drug delivery systems possess several advantages, such as high drug capacity, adjustably specific targeting capability, and stable structure, which endow nanomaterials great application potential in cancer therapy. However, even though the nanomaterials have been widely used in cancer therapy, there are still few reviews on their application in esophageal cancer, and systematical overview and analysis are deficient. Herein, we overviewed the application of nanodrug systems in therapy and diagnosis of esophageal cancer and summarized some representative case of their application in diagnosis, chemotherapy, targeted drug, radiotherapy, immunity, surgery and new therapeutic method of esophageal cancer. In addition, the nanomaterials used for therapy of esophageal cancer complications, esophageal stenosis or obstruction and oesophagitis, are also listed here. Finally, the challenge and the future of nanomaterials used in cancer therapy were discussed.

Using Liquid Biopsy to Predict Relapse After Radiotherapy in Squamous Cell Head-Neck and Esophageal Cancer.

Circulating cell-free DNA (cfDNA) in the blood of cancer patients contains tumor-specific mutated genes and viral genome that can be identified and quantified as 'tumor-specific cfDNA' (circulating tumor DNA, ctDNA). Various technologies are available that offer reliable detection of ctDNA at a low concentration. Quantitative and qualitative analysis of ctDNA may be of prognostic and predictive value in oncology. Here, we present concisely the experience on the assessment of ctDNA levels and kinetics during therapy in the outcome of radiotherapy (RT) and chemo-radiotherapy (CRT) in squamous cell head-neck cancer and esophageal squamous cell cancer patients. The levels of circulating viral (human papilloma virus or Epstein-Barr) ctDNA, and levels of total, mutated or methylated ctDNA at diagnosis are linked with tumor burden and clinical aggressiveness, and may be of prognostic or even predictive value of RT/CRT efficacy. Persistent ctDNA levels after therapy seem to predict high rates of tumor relapse several months before radiological documentation. This can prove of value for the identification of subgroups of patients who could benefit from RT dose-escalation or consolidation chemotherapy and immunotherapy, a hypothesis that should be tested in clinical trials.

Feasibility study of adaptive radiotherapy for esophageal cancer using artificial intelligence autosegmentation based on MR-Linac.

We proposed a scheme for automatic patient-specific segmentation in Magnetic Resonance (MR)-guided online adaptive radiotherapy based on daily updated, small-sample deep learning models to address the time-consuming delineation of the region of interest (ROI) in the adapt-to-shape (ATS) workflow. Additionally, we verified its feasibility in adaptive radiation therapy for esophageal cancer (EC). Nine patients with EC who were treated with an MR-Linac were prospectively enrolled. The actual adapt-to-position (ATP) workflow and simulated ATS workflow were performed, the latter of which was embedded with a deep learning autosegmentation (AS) model. The first three treatment fractions of the manual delineations were used as input data to predict the next fraction segmentation, which was modified and then used as training data to update the model daily, forming a cyclic training process. Then, the system was validated in terms of delineation accuracy, time, and dosimetric benefit. Additionally, the air cavity in the esophagus and sternum were added to the ATS workflow (producing ATS+), and the dosimetric variations were assessed. The mean AS time was 1.40 [1.10-1.78 min]. The Dice similarity coefficient (DSC) of the AS model gradually approached 1; after four training sessions, the DSCs of all ROIs reached a mean value of 0.9 or more. Furthermore, the planning target volume (PTV) of the ATS plan showed a smaller heterogeneity index than that of the ATP plan. Additionally, V5 and V10 in the lungs and heart were greater in the ATS+ group than in the ATS group. The accuracy and speed of artificial intelligence-based AS in the ATS workflow met the clinical radiation therapy needs of EC. This allowed the ATS workflow to achieve a similar speed to the ATP workflow while maintaining its dosimetric advantage. Fast and precise online ATS treatment ensured an adequate dose to the PTV while reducing the dose to the heart and lungs.

Immunotherapy with or without radiotherapy in late-line treatment for metastatic esophageal cancer: A real-world study.

e16054 Background: Single-agent immunotherapy is the standard second-line treatment of advanced esophageal cancer, however, the efficiency of single-agent immunotherapy is low, about 10-30%. Synergistic effects of radiation and immunotherapy have been demonstrated. This study evaluated the efficacy and safety of late-line immunotherapy combined with radiotherapy in patients with advanced esophageal cancer. Methods: We conducted a retrospective analysis of 85 patients treated at West China Hospital of Sichuan University between 2019 and 2022, all of whom had stage IV esophageal cancer and were treated with immunotherapy as a late-line therapy. We used Kaplan-Meier analysis to calculate progression-free survival (PFS), overall survival (OS). Results: After analysis, there were no differences in the baseline clinical characteristics such as age, gender, ECOG score, tumor location, and TNM stage. However, the proportion of received chemotherapy or targeted therapy may be greater in the non-radiotherapy group.38 were in the radiotherapy (RT) group and received radiotherapy to 41 lesion sites, and 47 were in the non-radiotherapy(non-RT) group. The most frequent radiotherapy organ sites were lymph nodes (14/41), esophagus (11/41), lung (9/41), bone (5/41), and brain (2/41) (three patients had irradiated metastases in two locations). The most common type of RT is conventional radiation therapy (31/41), including 12 radiotherapy courses of radical dose (50-60Gy, 28-30 fractions) and 18 radiotherapy courses of palliative dose (9-45Gy, 3-23 fractions). Then stereotactic body radiotherapy (10/41), (24-45Gy, 3-5 fractions). K-M analysis showed a median PFS in the RT group (16.7 months [95% CI 11.70-21.71 months]) vs. (6.97 months [95% CI 3.81-10.12 months], P = 0.014) in the non-RT group. And the median OS for the RT group was 24.4 months [95% CI 16.28-32.52 months] compared with 17.47 months [95% CI 15.11-19.83 months] (P = 0.039) for the non-RT group. The ORR of the RT group was 29.7% [95% CI, 14.3–45.2%] and 8.3% [95% CI, 2–16.4%] in the non-RT group(p=0.01). Univariate and multivariate analyses show that RT was an independent prognostic factor for OS. Overall, 33.3% and 32.5% of patients in the RT and non-RT groups, respectively, experienced at least one grade 3-4 treatment-related adverse event, with the most common treatment-related adverse reaction being myelosuppression, no differences in adverse effects between groups. Conclusions: In this study, late-line immunotherapy combined with radiotherapy for advanced esophageal cancer can improve the objective response rate and survival with manageable side effects. Although the limitations of retrospective studies should be taken into account, the findings still suggest that patients benefit from immunotherapy combined with radiotherapy, and more data are needed to assess the impact of radiation therapy on these patients.

Chemoradiotherapy with concurrent durvalumab for the palliative treatment of oligometastatic esophageal and gastroesophageal carcinoma with dysphagia: A single arm phase 2 clinical trial, PALEO.

TPS4172 Background: Many patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. While multiple therapies are available, there is no accepted standard or sequence of therapies to both relieve dysphagia and control distant disease. Our preceding Phase I clinical trial showed that a 2 week hypofractionated chemoradiotherapy (CRT) protocol (30Gy/10# with concurrent weekly carboplatin and paclitaxel) is well tolerated and provides rapid dysphagia relief. Immune checkpoint inhibition has activity in esophageal and gastroesophageal (GEJ) cancer and concurrent radiotherapy may improve T cell priming through tumor antigen release. In PALEO, patients begin durvalumab concurrent with primary tumor CRT, and receive stereotactic body radiotherapy (SBRT) (24Gy/3#) to a single metastasis to maximize the breadth of tumor antigen exposure. Tissue and blood-based studies are planned to identify biomarkers for response, including immunosequencing to test for post-radiotherapy expansion in T cell receptor diversity. Methods: Eligible patients have biopsy-proven esophageal or GEJ cancer, either squamous cell or adenocarcinoma histology, with oligometastatic (1-5 metastases on FDG-PET scan outside the primary tumor radiotherapy field) or locoregionally advanced disease unsuitable for surgery, dysphagia (Mellow score &gt;0), and ECOG PS 0-2. Key exclusion criteria are prior treatment, tumor HER2 positivity, prior thoracic radiotherapy, tracheo-esophageal fistula, esophageal stent in situ and contraindications to immunotherapy. Patients begin durvalumab 1500mg q4w with CRT to the primary tumour (30Gy/10# with weekly carboplatin AUC2 and paclitaxel 50mg/m2), and continuing to disease progression, unacceptable toxicity or 2 years. SBRT to one metastasis (24Gy/3#) is delivered in week 7. Trial primary endpoint is progression free survival rate at 6 months (PFS6) with the aim to rule out a PFS6 rate of 50% in favor of 67.5%, with 80% power and a one-sided 0.05 significance level. Secondary endpoints include dysphagia relief, nutritional status change (patient weight, removal of enteral feeding tubes, PG-SGA score), quality of life, response rate, toxicity, overall survival and exploratory translational endpoints. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG) for conduct at 8 sites in Australia and New Zealand. 6 of planned 54 patients have been enrolled. ACTRN12619001371189. Clinical trial information: Clinical trial information: ACTRN12619001371189 .

Progression of coronary artery calcification after radiation therapy for esophageal cancer.

Advances in cancer treatment have resulted in increased attention toward potential cardiac complications, especially following treatment for esophageal cancer, which is associated with a risk of coronary artery disease. As the heart is directly irradiated during radiotherapy, coronary artery calcification (CAC) may progress in the short term. Therefore, we aimed to investigate the characteristics of patients with esophageal cancer that predispose them to coronary artery disease, CAC progression on PET-computed tomography and the associated factors, and the impact of CAC progression on clinical outcomes. We retrospectively screened 517 consecutive patients who received radiation therapy for esophageal cancer from our institutional cancer treatment database between May 2007 and August 2019. CAC scores were analyzed clinically for 187 patients who remained by exclusion criteria. A significant increase in the Agatston score was observed in all patients (1 year: P = 0.001*, 2 years: P < 0.001*). Specifically for patients receiving middle-lower chest irradiation (1 year: P = 0.001*, 2 years: P < 0.001*) and those with CAC at baseline (1 year: P = 0.001*, 2 years: P < 0.001*), a significant increase in the Agatston score was observed. There was a trend for a difference in all-cause mortality between patients who had irradiation of the middle-lower chest ( P = 0.053) and those who did not. CAC can progress within 2 years after the initiation of radiotherapy to the middle or lower chest for esophageal cancer, particularly in patients with detectable CAC before radiotherapy initiation.

Experimental study of 131I-caerin 1.1 and 131I-c(RGD)2 for internal radiation therapy of esophageal cancer xenografts

ObjectiveThe aim of this study was to analyze and compare the therapeutic effects of 131I-caerin 1.1 and 131I-c(RGD)2 on TE-1 esophageal cancer cell xenografts. Methods(1) The in vitro antitumor effects of the polypeptides caerin 1.1 and c(RGD)2 were verified by MTT and clonogenic assays. 131I-caerin 1.1 and 131I-c(RGD)2 were prepared by chloramine-T (Ch-T) direct labeling, and their basic properties were measured. The binding and elution of 131I-caerin 1.1, 131I-c(RGD)2, and Na131I (control group) in esophageal cancer TE-1 cells were studied through cell binding and elution assays. (2) The antiproliferative effect and cytotoxicity of 131I-caerin 1.1, 131I-c(RGD)2, Na131I, caerin 1.1 and c(RGD)2 on TE-1 cells were detected by Cell Counting Kit-8 (CCK-8) assay. (3) A nude mouse esophageal cancer (TE-1) xenograft model was established to study and compare the efficacy of 131I-caerin 1.1 and 131I-c(RGD)2 in internal radiation therapy for esophageal cancer. Results(1) Caerin 1.1 inhibited the in vitro proliferation of TE-1 cells in a concentration-dependent manner, with an IC50 of 13.00 µg/mL. The polypeptide c(RGD)2 had no evident inhibitory effect on the in vitro proliferation of TE-1 cells. Therefore, the antiproliferative effects of caerin 1.1 and c(RGD)2 on esophageal cancer cells were significantly different (P < 0.05). The clonogenic assay showed that the clonal proliferation of TE-1 cells decreased as the concentration of caerin 1.1 increased. Compared with the control group (drug concentration of 0 µg/mL), the caerin 1.1 group showed significantly lower clonal proliferation of TE-1 cells (P < 0.05). (2) The CCK-8 assay showed that 131I-caerin 1.1 inhibited the in vitro proliferation of TE-1 cells, while 131I-c(RGD)2 had no evident inhibitory effect on proliferation. The two polypeptides showed significantly different antiproliferative effects on esophageal cancer cells at higher concentrations (P < 0.05). Cell binding and elution assays showed that 131I-caerin 1.1 stably bound to TE-1 cells. The cell binding rate of 131I-caerin 1.1 was 15.8 % ± 1.09 % at 24 h and 6.95 % ± 0.22 % after 24 h of incubation and elution. The cell binding rate of 131I-c(RGD)2 was 0.06 % ± 0.02 % at 24 h and 0.23 % ± 0.11 % after 24 h of incubation and elution. (3) In the in vivo experiment, 3 days after the last treatment, the tumor sizes of the phosphate-buffered saline (PBS) group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 68.29 ± 2.67 mm3, 61.78 ± 3.58 mm3, 56.67 ± 5.65 mm3, 58.88 ± 1.71 mm3, 14.40 ± 1.38 mm3, and 60.14 ± 0.47 mm3, respectively. Compared with the other treatment groups, the 131I-caerin 1.1 group had significantly smaller tumor sizes (P < 0.001). After treatment, the tumors were isolated and weighed. The tumor weights in the PBS group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 39.50 ± 9.54 mg, 38.25 ± 5.38 mg, 38.35 ± 9.53 mg, 28.25 ± 8.50 mg, 9.50 ± 4.43 mg, and 34.75 ± 8.06 mg, respectively. The tumor weights in the 131I-caerin 1.1 group were significantly lighter than those in the other groups (P < 0.01). Conclusion131I-caerin 1.1 has tumor-targeting properties, is capable of targeted binding to TE-1 esophageal cancer cells, can be stably retained in tumor cells, and has an evident cytotoxic killing effect, while 131I-c(RGD)2 has no evident cytotoxic effect. 131I-caerin 1.1 better suppressed tumor cell proliferation and tumor growth than pure caerin 1.1, 131I-c(RGD)2, and pure c(RGD)2.

PO-1390 Definitive radiotherapy in T1N0M0 esophageal cancer: a multicenter retrospective study (KROG 21-10)

PO-1390 Definitive radiotherapy in T1N0M0 esophageal cancer: a multicenter retrospective study (KROG 21-10)

Association of survival with adjuvant radiotherapy for pN0 esophageal cancer

Introduction: This study was conducted to elucidate the link between adjuvant radiotherapy and survival in pathologic node-negative (pN0) esophageal cancer patients with upfront esophagectomy. Methods: From 2000 to 2016, patients with pN0 esophageal cancer who underwent upfront esophagectomy were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The association of high-risk covariates with survival after adjuvant radiotherapy was evaluated using propensity score matching and multivariate analysis. Results: We identified 3197 patients, 321 (10.0%) underwent postoperative radiotherapy and 2876 (90.0%) underwent esophagectomy alone. In the unmatched cohort, postoperative radiotherapy was associated with a statistically significant but modest absolute decrease in survival outcomes (P < 0.001). In the matched cohort, the survival differences disappeared. Additionally, adjuvant radiotherapy was linked to a 5-year overall survival (OS) benefit for patients with the pT3-4N0 disease (34.8% vs. 27.7%; P = 0.008). Adjuvant radiotherapy for pT3-4N0 disease with tumor length ≥3 cm, adenocarcinoma, and evaluated lymph node count <12 was shown to independently function as a risk factor for improved OS, as per a multivariate analysis (P < 0.01). Conclusions: This population-based trial showed that high-risk patients with pT3-4N0 esophageal cancer had better OS following upfront esophagectomy followed by radiotherapy therapy. This discovery may have major significance in the use of adjuvant radiotherapy following upfront esophagectomy in patients with pN0 esophageal cancer.

Analysis of particle therapy registries based on a unified treatment policy for esophageal cancer.

This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69years (range: 41-88years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908days (range: 76-1669days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.

Intrafraction motion analysis in online adaptive radiotherapy for esophageal cancer.

Intrafraction motion during magnetic resonance (MR)-guided dose delivery of esophageal cancer tumors was retrospectively analyzed. Deformable image registration of cine-MR series resulted in gross tumor volume motion profiles in all directions, which were subsequently filtered to isolate respiratory and drift motion. A large variability in intrafraction motion patterns was observed between patients. Median 95% peak-to-peak motion was 7.7 (3.7 - 18.3) mm, 2.1 (0.7 - 5.7) mm and 2.4 (0.5 - 5.6) mm in cranio-caudal, left-right and anterior-posterior directions, relatively. Furthermore, intrafraction drift was generally modest (<5mm). A patient specific approach could lead to very small margins (<3mm) for most patients.