Radiotherapy For Esophageal Carcinoma Research Articles

Dosimetric rationale and preliminary experience in proton plus carbon-ion radiotherapy for esophageal carcinoma: a retrospective analysis

BackgroundConcurrent chemoradiotherapy has been standard of care for unresectable esophageal carcinoma. There were no reports on proton radiotherapy (PRT) plus carbon-ion radiotherapy (CIRT) with pencil beam scanning (PBS) for esophageal carcinoma. This study evaluated the tolerability and efficiency of proton and sequential carbon-ion boost radiotherapy for esophageal carcinoma.MethodsFrom April 2017 to July 2020, 20 patients with primary esophageal carcinoma at stages II–IV were treated with PRT plus sequential CIRT with PBS. A median relative biological effectiveness-weighted PRT dose of 50 Gy in 25 fractions, and a sequential CIRT dose of 21 Gy in 7 fractions were delivered. Respiratory motion management was used if the tumor moved > 5 mm during the breathing cycle. A dosimetric comparison of photon intensity-modulated radiotherapy (IMRT), PRT, and CIRT was performed. The median times and rates of survivals were estimated using the Kaplan–Meier method. Comparison of the dose-volume parameters of the organs at risk employed the Wilcoxon matched-pairs test.ResultsTwenty patients (15 men and 5 women, median age 70 years) were included in the analysis. With a median follow-up period of 25.0 months, the 2-year overall survival and progression-free survival rates were 69.2% and 57.4%, respectively. The patients tolerated radiotherapy and chemotherapy well. Grades 1, 2, 3, and 4 acute hematological toxicities were detected in 25%, 30%, 10%, and 30% of patients, respectively. Grades 3–5 acute non-hematological toxicities were not observed. Late toxicity events included grades 1, 2, and 3 in 50%, 20%, and 10% (pulmonary and esophageal toxicity in each) of patients. Grades 4–5 late toxicities were not noted. PRT or CIRT produced lower doses to organs at risk than did photon IMRT, especially the maximum dose delivered to the spinal cord and the mean doses delivered to the lungs and heart.ConclusionsPRT plus CIRT with PBS appears to be a safe and effective treatment for esophageal carcinoma. PRT and CIRT delivered lower doses to organs at risk than did photon IMRT. Further investigation is warranted.

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.

Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence

PurposeFor treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy. Material and methodsWe reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC. ResultsThe lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ2=264.776, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ2=313.600, P=0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage. ConclusionsThe main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.

Demonstration of quasi-real-time intrafractional motion in esophageal cancer radiotherapy provided by ExacTrac X-ray snap verification.

To investigate the following hypotheses: (1) ExacTrac X-ray Snap Verification (ET-SV) is an alternative to CBCT for positioning patients with esophageal carcinoma (EC), (2) ET-SV can detect displacement in EC patients during radiotherapy (RT) and (3) EC patients can be feasibly monitored in quasi-real-time with ET-SV during RT. Anthropomorphic phantoms and 13 patients were included in this study. CBCT and ET-SV were both implemented before treatment delivery to detect displacement, and their correction results were compared. For the patient tests, positional correction in 3 translational directions and the yaw direction were applied using the ET-SV correction results. The residual error was detected immediately using ET-SV. Finally, to acquire the intrafractional motion, ET-SV was implemented when the gantry was at 0°, 90°, 180° and 270°, respectively. In phantom tests, the maximum value of the difference in displacement between the CBCT and ET systems was 1.16 mm for translation and 0.31° for yaw. According to Bland-Altman analysis of the patient test results, 5% (5/98), 5% (5/98), 5% (5/98), and 4% (4/98) of points were beyond the upper and lower limits of agreement in the AP, SI, LR and yaw directions, respectively. The mean residual error was -0.482 mm, 1.215 mm, 1.0 mm, -0.487°, 0.105°, and 0.003° in the AP, SI, LR, pitch, roll and yaw directions, respectively. The intrafractional displacement ranged from -0.21 mm to 0 mm for translation and from -0.63° to 0.21° for rotation. The mean total translational error for intrafractional motion increased from 0.47 mm to 1.14 mm during the treatment. The accuracy of ET-SV for EC RT positional correction is comparable to that of CBCT. Thus, Quasi-real-time intrafractional monitoring can be used to detect EC patient displacement during radiotherapy.

Radiobiological Comparison of Acuros External Beam and Anisotropic Analytical Algorithm on Esophageal Carcinoma Radiotherapy Treatment Plans.

ObjectiveThe present study aimed to investigate the dose differences and radiobiological assessment between Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB) with its 2 calculation models, namely, dose-to-water (AXB-Dw) and dose-to-medium (AXB-Dm), on esophageal carcinoma radiotherapy treatment plans.Materials and methodsThe AXB-Dw and AXB-Dm plans were generated by recalculating the initial 66 AAA plans using the AXB algorithm with the same monitor units and beam parameters as those in the original plan. The dosimetric and radiobiological assessment parameters were calculated for the planning target volume (PTV) and organs at risk (OARs). The gamma agreement for the PTV and the correlation between it and the volume of the air cavity and bone among the different algorithms were compared simultaneously. The dose discrepancy between the theoretical calculation and treatment planning system (TPS) when switching from AXB-Dm to AXB-Dw was analyzed according to the composition of the structures.ResultsThe PTV dose of AXB-Dm plans was significantly smaller than that of the AAA and AXB-Dw plans (P < .05), except for D2. The difference values for AAA vs AXB-Dm (∆Dx,(AAA-AXB,Dm)) and AXB-Dw vs AXB-Dm (∆Dx,(AXB,Dw-AXB,Dm)) were 1.94% [1.27%, 2.64%] and 1.95% [1.56%, 2.27%], respectively. For the spinal cord and heart, there were obvious differences between the AAA vs AXB-Dm (spinal cord: 1.15%, heart: 2.89%) and AXB-Dw vs AXB-Dm (spinal cord: 1.88%, heart: 3.25%) plans. For the lung, the differences between AAA vs AXB-Dm and AAA vs AXB-Dw were significantly larger than those of AXB-Dm vs AXB-Dw. Compared to the case of AAA and AXB-Dw, the decrease in biologically effective dose (BED10, ) of AXB-Dm due to dose non-uniformity exceeded 6.5%, even for a small . The average values of equivalent uniform dose in the AAA, AXB-Dw, and AXB-Dm plans were 52.03±.39 Gy, 52.24 ± .81 Gy, and 51.13 ± .47 Gy, respectively. The tumor control probability (TCP) results for PTV in the AAA, AXB-Dw, and AXB-Dm plans were 62.29 ± 1.57%, 62.82 ± 1.69%, and 58.68±1.88%, respectively. With the 2%/2 mm and 3%/3 mm acceptance criteria, the mean values of , , and were 87.24, 63.3, and 64.81% vs 97.86, 91.77, and 89.25%, respectively. The dose discrepancy between the theoretical calculation and TPS when switching from AXB-Dm to AXB-Dw was approximately 1.63%.ConclusionsThe AAA and AXB-Dw algorithms overestimated the radiobiological parameters when the tumor particularly consisted of nonuniform tissues. A relatively small dose difference could cause a significant reduction in the corresponding TCP. Dose distribution algorithms should be carefully chosen by physicists and oncologists to improve tumor control, as well as to optimize OARs protection.

Knockdown long non-coding RNA HCP5 enhances the radiosensitivity of esophageal carcinoma by modulating AKT signaling activation

ABSTRACT Recently, long noncoding RNAs (lncRNAs) have been revealed to participate in cancer therapy. Especial in tumor radiotherapy, lncRNAs usually could enhance or restrict the radiosensitivity in different ways. LncRNA HCP5 is highly expressed in esophageal cancer and influenced the malignant behaviors of esophageal cancer cells. However, this study dedicates to clarify if lncRNA HCP5 affects the radiosensitivity of esophageal carcinoma. The expression levels of HCP5 in esophageal cancer and adjacent noncancerous tissue were first analyzed on the TCGA database and then detected by qRT-PCR. The related functional experiments were used to investigate whether the radiosensitivity of esophageal squamous cell carcinoma was affected by the inhibition of HCP5. The expression results showed HCP5 is upregulated in esophageal cancers compared to the normal tissues. Meanwhile, knockdown HCP5 further suppressed the proliferation and promoted the apoptosis of esophageal cancer cells treated with a 2 Gy dose of radiotherapy. Moreover, we uncovered that knockdown HCP5 eliminated radiotherapy resistance by modulating the miR-216a-3p/PDK1 axis to inhibit the AKT activation. Finally, rescue experiments pointed that lowering the miR-216a-3p expression weakened the inhibition effect of knockdown HCP5 on cells treated with radiotherapy. To summary, our results indicate that HCP5 is involved in esophageal carcinoma radiotherapy and knockdown HCP5 enhances the radiosensitivity of esophageal carcinoma by modulating AKT signaling activation.

Ultrasound-stimulated microbubbles contributes to radiotherapy in esophageal carcinoma.

This study aimed to explore the effect of ultrasound-stimulated microbubbles (USMBs) on tumor radiosensitivity in esophageal carcinoma (EC). The human EC cell line KYSE-510 and human umbilical vein endothelial cells (HUVECs) were exposed to radiation alone or in combination with USMBs. CCK-8, colony formation, and EdU assays were used to determine cell viability and proliferation. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. Western blotting showed that the protein levels were associated with apoptosis, epithelial-mesenchymal transition (EMT), and angiogenesis. An endothelial tube-forming assay was used to detect the angiogenic activity of HUVECs. Xenograft experiments were used to examine the effect of USMBs on EC radiosensitivity in vivo. The expression of Ki-67 in tumors was detected using immunohistochemistry. USMBs enhanced the suppressive effect of radiation on proliferation, migration, invasion, and EMT, and promoted radiation-induced apoptosis in EC cells in vitro. Angiogenesis in EC was suppressed by radiation and further inhibited by the combination of radiation and USMBs. In vivo experiments revealed that USMBs increased the radiosensitivity of ECs to tumor growth. Collectively, USMBs enhanced the effects of radiotherapy in esophageal carcinoma.

Increased Esophageal Perforation After Combination of Anti-PD-1 Immunotherapy With Radiotherapy for Esophageal Carcinoma

<h3>Purpose/Objective(s)</h3> Recent studies demonstrated that immunotherapy can improve the survival of patients with locally advanced and metastatic esophageal carcinoma. Combination of anti-programmed death receptor-1 (PD-1) immunotherapy and radiotherapy (RT) was a promising therapeutic strategy. Therefore, a number clinical trials are underway to study the effect of anti-PD-1 immunotherapy combined with RT in patients with esophageal carcinoma. Esophageal perforation is a severe side-effect of esophageal radiation, but there is limited information about the toxicity profile of their combined treatment. We reviewed our experience to assess the impact of anti-PD-1 immunotherapy with or without antiangiogenic tyrosine kinase inhibitors (TKIs) in combination with esophageal RT on the risk of esophageal perforation for patients with locally advanced and metastatic esophageal carcinoma. <h3>Materials/Methods</h3> Patient and treatment characteristics were collected on all consecutive patients from November 2017 to December 2020 at our institution who were treated with esophageal RT, with or without anti-PD-1 immunotherapy and/or antiangiogenic TKIs (e.g., anlotinib or apatinib). Clinical, radiologic, and endoscopic features of perforation were collected. Associations among perforation incidence and therapy received were examined with Fisher's exact test as were associations between perforation features and outcomes. <h3>Results</h3> Of 180 patients with locally advanced and metastatic EC who received esophageal RT with palliative or curative intent, perforation developed in 13 (7.2%). Fifty (27.8%) patients were treated with anti-PD-1 immunotherapy, 13 (7.2%) with antiangiogenic TKIs, and 8 (4.4%) received both anti-PD-1 immunotherapy and antiangiogenic TKIs. The incidence of perforation was higher in cases with and without anti-PD-1 immunotherapy (9 of 50 [18.0%] vs 4 of 130 [3.1%]; respectively, <i>P</i> = 0.002). Among the nine patients with anti-PD-1 immunotherapy who developed perforation following RT, 2 of 27 (7.4%) received anti-PD-1 immunotherapy only before RT, and 7 of 23 (30.4%) received anti-PD-1 immunotherapy after RT (including 4 in combination with antiangiogenic TKIs). Time to onset of perforation from ranged from 16 days to 189 days during anti-PD-1 immunotherapy in the 7 patients who received anti-PD-1 immunotherapy after RT. <h3>Conclusion</h3> In conclusion, this is the first report of esophageal perforation after treatment with anti-PD-1 immunotherapy and RT. We observed a higher incidence of perforation when anti-PD-1 immunotherapy and esophageal RT were administered in patients with esophageal carcinoma, especially anti-PD-1 immunotherapy administered after RT. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of perforation in patients treated with anti-PD-1 immunotherapy after esophageal RT, and careful monitoring for perforation is recommended.

Clinical Study of Radiotherapy for Esophageal Carcinoma

Clinical Study of Radiotherapy for Esophageal Carcinoma

Guidelines for Radiotherapy of Esophageal Carcinoma (2020 Edition)

Guidelines for Radiotherapy of Esophageal Carcinoma (2020 Edition)

Predicting the effects of radiotherapy based on diffusion kurtosis imaging in a xenograft mouse model of esophageal carcinoma.

The aim of the present study was to assess the predictive value of diffusion kurtosis imaging (DKI) on the effects of radiotherapy in a xenograft model of esophageal cancer. A total of 40 tumor-bearing mice, established by injection of Eca-109 cells in nude mice, were used. The experimental group (n=24) received a single dose of 15 Gy (6 MV by X-ray), and the control group (n=16) did not receive any treatment. Tumor volume, apparent diffusion coefficient (ADC), mean kurtosis (MK) and mean diffusivity (MD) of the two groups were compared, and the expression of aquaporin (AQP) 3 and necrosis ratio at matched time points in xenografts were also observed. There was a significant difference between the two groups from the 7th day of radiotherapy onwards; the xenograft volume of the experimental group was significantly smaller compared with the control group (P<0.05). On the 3rd day, the ADC and MD of the experimental group was significantly higher compared with the control group, and MK was significantly lower compared with the control group (P<0.05). On the 3rd day, AQP3 expression in the experimental group was lower compared with the control group, and the proportion of necrotic cells was higher compared with the control group (P<0.05). Single large fraction dose radiotherapy inhibited the growth of a xenografted esophageal tumor. Changes in ADC, MK and MD were observed prior to morphological changes in the tumor. The change in AQP3 expression and necrosis ratio was in also agreement with the DKI parameters assessed. DKI may thus provide early predictive ability on the effect of radiotherapy in esophageal carcinoma.

Comparison of gross target volumes based on four-dimensional CT, positron emission tomography-computed tomography, and magnetic resonance imaging in thoracic esophageal cancer.

PurposeThe application value of 18F‐FDG PET‐CT combined with MRI in the radiotherapy of esophageal carcinoma was discussed by comparing the differences in position, volume, and the length of GTVs delineated on the end‐expiration (EE) phase of 4DCT, 18F‐FDG PET‐CT, and T2W‐MRI.MethodsA total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18F‐FDG PET‐CT, and MRI simulation for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTVCT and GTV50% were delineated on 3DCT and the EE phase of 4DCT images, respectively. The GTV based on PET‐CT images was determined by thresholds of SUV ≥ 2.5 and designated as GTVPET2.5. The images of T2‐weighted sequence and diffusion‐weighted sequence were referred as GTVMRI and GTVDWI, respectively. The length of the abnormality seen on the 4DCT, PET‐CT, and DWI was compared.ResultsGTVPET2.5 was significantly larger than GTV50% and GTVMRI (P = .000 and 0.008, respectively), and the volume of GTVMRI was similar to that of GTV50% (P = .439). Significant differences were observed between the CI of GTVMRI to GTV50% and GTVPET2.5 to GTV50% (P = .004). The CI of GTVMRI to GTVCT and GTVPET2.5 to GTVCT were statistically significant (P = .039). The CI of GTVMRI to GTVPET2.5 was significantly lower than that of GTVMRI to GTV50%, GTVMRI to GTVCT, GTVPET2.5 to GTV50%, and GTVPET2.5 to GTVCT (P = .000‐0.021). Tumor length measurements by endoscopy were similar to the tumor length as measured by PET and DWI scan (P > .05), and there was no significant difference between the longitudinal length of GTVPET2.5 and GTVDWI (P = .072).ConclusionThe volumes of GTVMRI and GTV50% were similar. However, GTVMRI has different volumes and poor spatial matching compared with GTVPET2.5.The MRI imaging could not include entire respiration. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. Utilization of DWI in treatment planning for esophageal cancer may provide further information to assist with target delineation. Further studies are needed to determine if this technology will translate into meaningful differences in clinical outcome.

Acute Toxicities and Short-Term Patient Outcomes After Intensity-Modulated Proton Beam Radiation Therapy or Intensity-Modulated Photon Radiation Therapy for Esophageal Carcinoma: A Mayo Clinic Experience

PurposeIntensity modulated proton beam radiation therapy (IMPT) has a clinically significant dosimetric advantage over intensity modulated photon radiation therapy (IMRT) for the treatment of patients with esophageal cancer, particularly for sparing the heart and lungs. We compared acute radiation therapy–related toxicities and short-term clinical outcomes of patients with esophageal cancer who received treatment with IMPT or IMRT. Methods and MaterialsWe retrospectively reviewed the electronic health records of consecutive adult patients with esophageal cancer who underwent concurrent chemoradiotherapy with IMPT or IMRT in the definitive or neoadjuvant setting from January 1, 2014, through June 30, 2018, with additional follow-up data collected through January 31, 2019. Treatment-related toxicities were evaluated per the Common Terminology Criteria for Adverse Events, version 4. Survival outcomes were estimated with the Kaplan-Meier method. ResultsA total of 64 patients (32 per group) were included (median follow-up time: 10 months for IMPT patients vs 14 months for IMRT patients). The most common radiation therapy regimen was 45 Gy in 25 fractions, and 80% of patients received a simultaneous integrated boost to a median cumulative dose of 50 Gy. Similar numbers of IMPT patients (n = 15; 47%) and IMRT patients (n = 18; 56%) underwent surgery (P = .07), with no difference in pathologic complete response rates (IMPT: n = 5; 33% vs IMRT: n = 7; 39%; P = .14). At 1 year, the clinical outcomes also were similar for IMPT and IMRT patients, respectively. Local control was 92% versus 84% (P = .87), locoregional control 92% versus 80% (P = .76), distant metastasis–free survival 87% versus 65% (P = .08), progression-free survival 71% versus 45% (P = .15), and overall survival 74% versus 71% (P = .62). The rate of acute treatment–related grade 3 toxicity was similar between the groups (P = .71). ConclusionsIn our early experience, IMPT is a safe and effective treatment when administered as part of definitive or trimodality therapy. Longer follow-up is required to evaluate the effectiveness of IMPT.

Mortality from heart disease following radiotherapy in esophageal carcinoma: a retrospective cohort study in US SEER cancer registry.

BackgroundRecently, multiple studies have focused on cardiac toxicity induced by radiation, particularly in patients with breast carcinoma. However, in most circumstances, the radiation intensity is much higher for the heart in patients with esophageal carcinoma. This study aimed to investigate whether cardiac toxicity is related to radiation and distinguish the types of patients who are more susceptible to cardiac death.MethodsWe analyzed 8,210 esophageal cancer survivors who were involved in the US Surveillance Epidemiology and End Results (SEER) cancer program. Descriptive statistics were used to demonstrate the disease characteristics in radiation therapy (RT) and non-RT groups. Cox hazard proportional regression and Kaplan-Meier method were applied to determine independent risk factors of cardiac death.ResultsThe most important risk factors determining heart death were age (HR, 14.297; 95% CI: 9.174–22.283) and radiation (HR, 1.952; 95% CI: 1.684–2.263). The radiotherapy performed in the middle (HR, 1.872; 95% CI: 1.464–2.395) and lower thoracic segment of the esophagus (HR, 1.539; 95% CI: 1.464–1.772) was associated with an increased risk of cardiogenic death, which occurred since the first year after diagnosis. Compared with RT in postoperative group (HR, 0.48; 95% CI, 0.37–0.62), patients in preoperative group had a significantly increased survival rate.ConclusionsCardiogenic death is closely related to RT in esophageal cancer patients. Age, radiation sequence and tumor sites are key factors influencing the cardiac death risk induced by radiotherapy. Early detection and prevention are necessary for the high-risk population.

Comparison of efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma.

BackgroundWe compared the efficacy, safety, and costs of hypofractionated radiotherapy (HFRT) and conventional fractionated radiotherapy (CFRT) for the neoadjuvant treatment of esophageal cancer.Materials and MethodsOverall, 110 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy from October 2002 to July 2017 were retrospectively included and divided into a HFRT group (42 patients received 30 Gray [Gy]/10 fractions for 2 weeks) and a CFRT group [68 patients received 40 Gy/20 fractions for 4 weeks]. Concurrent chemotherapy comprised cisplatin combined with either 5‐FU or taxane. Surgery was performed 3‐8 weeks after radiotherapy. We compared the outcomes, adverse events, and costs between the two groups.ResultsPathological downstaging was achieved in 78.6% of the HFRT group and 83.8% of the CFRT group (P = 0.612). Compared with the CFRT group, the HFRT group had similar pathological complete response (pCR) (33.3% vs 35.3%; P = 0.834), median overall survival (OS) (40.8 months vs 44.9 months; P = 0.772) and progression free survival (32.7 months vs 35.4 months; P = 0.785). The perioperative complication rates were also similar between the groups, but the treatment time and costs were significantly reduced in the HFRT group (P < 0.05). Finally, multivariate analysis identified cN0 stage, pathological downstaging and pCR as independent predictors of better OS.ConclusionPreoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost effective and less time consuming.

Biodegradable oesophageal stents: A potentially useful adjunct in the treatment of dysphagia in patients undergoing radiotherapy for oesophageal carcinoma

AbstractAim:Dysphagia is common in patients presenting with oesophageal malignancy. This study aimed to determine the clinical effectiveness of biodegradable stents to help with malignant dysphagia due to radiotherapy for oesophageal cancer and furthermore to establish the complication and re-intervention rates associated with their use.Methods:This was a retrospective, observational study of 22 patients between 2008 and 2013. Complications within 2 weeks and episodes of re-intervention required within 4 months of stent insertion prior to radiotherapy were recorded.Results:Pre-stent insertion, the mean O’Rourke dysphagia score was 3·5 (median 3, range 2–5). This improved to a mean score of 2·8 (median 3, range 1–4) 1–3 weeks following stent insertion. Complications occurred in seven patients (32%) in an immediate 2-week period, including: pain (2), dysphagia requiring dilatation (1), food obstruction not requiring intervention (1), food obstruction requiring intervention (2) and upper gastrointestinal bleed not requiring intervention (1). Re-intervention was required in 18% within a 4-month period.Findings:We propose that biodegradable oesophageal stents are safe and may have benefit over self-expanding metal stents. We recommend they are placed alongside a radiologically inserted gastrostomy in a combined procedure prior to radiotherapy planning.

Relationship between factors of gross tumor volume and locoregional failure of radical intensity-modulated radiation therapy for esophageal carcinoma

Objective Investigate the relationship between gross tumor volume (GTV)-related factors including GTV-T volume, the maximum thickness of the esophageal lesion plane and GTV-T volume/length(GTV-T volume divided by the length of the lesion calculated by the number of GTV-T layers) and the locoregional failure of radical intensity-modulated radiation therapy (IMRT) for esophageal carcinoma. Methods A total of 133 patients with esophageal cancer undergoing radical IMRT were enrolled. The factors related to GTV-T including GTV-T volume, the maximum thickness of the esophageal lesions, GTV-T volume/length were calculated. The relationship between GTV-T related factors and local recurrence of tumors was retrospectively analyzed. Results There was positively linear association between the locoregional failure rate of GTV-T and the volume of GTV-T. The volume of GTV-T tumor was 36 cm3, the maximum wall thickness was 2.5 cm, and the GTV-T volume/length was calculated as 5.3 cm2. These critical values could be utilized to predict the risk of locoregional failure of IMRT for esophageal carcinoma. Conclusions The GTV-T factors can be adopted to predict the local control and the risk of locoregional failure of radical IMRT for esophageal carcinoma to certain extent. Key words: Esophageal carcinoma/radiotherapy; Intensity-modulated radiation therapy; Gross tumor volume; Wall thickness

Acute Toxicities and Short-Term Follow-up of Patients Treated with Pencil-Beam Scanning Proton Beam Radiation Therapy for Esophageal Carcinoma: A Single-Center Experience

Acute Toxicities and Short-Term Follow-up of Patients Treated with Pencil-Beam Scanning Proton Beam Radiation Therapy for Esophageal Carcinoma: A Single-Center Experience

Comparative study between simultaneous integrated and sequential boost using intensity-modulated radiotherapy for esophageal carcinoma

Objective To compare the clinical efficacy between simultaneous integrated boost (SIB) and sequential boost (SB) using intensity-modulated radiotherapy (IMRT), and investigate the long-term clinical efficacy and adverse events of SIB-IMRT in combination with chemotherapy in the treatment of esophageal cancer. Methods Clinical data of 330 patients diagnosed with esophageal cancer undergoing radical chemoradiotherapy in Fourth Hospital of Hebei University from January 2006 to December 2015 were respectively analyzed. All patients were assigned into the SIB-IMRT (n=135) and SB-IMRT groups (n=195). All patients received definitive radiotherapy with elective nodal irradiation (ENI). After the propensity score matching (PSM), 105 patients were enrolled in each group. Kaplan-Meier method was used to survival analysis. Cox model was used to multivariate prognostic analysis. Results Prior to PSM, the 1-, 3-and 5-year local control rates were 80.1%, 58.3%, 46.7% and 72.1%, 44.9%, 40.5% in the SIB-IMRT and SB-IMRT groups (P=0.050), and the 1-, 3-and 5-year OS rates were 81.4%, 51.9%, 43.5% and 80.5%, 37.9%, 22.3%(P=0.014), respectively. After the PSM, the 1-, 3-and 5-year LC rates were 80.2%, 54.2%, 43.9% and 75.5%, 47.2%, 41.2%(P=0.264), and the 1-, 3-and 5-year OS rates were 78.9%, 49.0%, 40.8% and 83.3%, 41.7%, 24.8%(P=0.265), respectively. Multivariate analysis demonstrated that TNM staging was an independent prognostic factor in the SIB-IMRT group, whereas TNM staging and chemotherapy served as the independent prognostic factors in the SB-IMRT group. Stratified analysis revealed that the LC rate in the SIB-IMRT was significantly higher than that in the SB-IMRT group when radiotherapy alone was performed (P=0.018). The OS rate in the SIB-IMRT group was equally higher compared with that in the SB-IMRT group. Conclusions The LC and OS rates are almost identical after SB-IMRT and SIB-IMRT in the treatment of esophageal cancer, whereas the prognostic survival in the SIB-IMRT group is significantly longer compared with that in the SB-IMRT group during radiotherapy alone. The findings remain to be validated by multi-center investigations with a large sample size. Key words: Esophageal neoplasms/intensity-modulated radiotherapy; Simultaneous integrated boost; Sequential boost; Prognosis

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.