Inoperable Esophageal Carcinoma Research Articles

First-line induction or consolidation chemotherapy combined with concurrent chemoradiotherapy for esophageal squamous cell carcinoma.

The RTOG 85-01 trial established that definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for inoperable, locally advanced esophageal carcinoma, as well as for patients who decline surgery. The present study aims to compare the impact of three treatment modalities, CCRT, induction chemotherapy (ICT) followed by CCRT (ICT + CCRT), and CCRT followed by consolidation chemotherapy (CCT) (CCRT + CCT), on the survival of patients with inoperable esophageal squamous cell carcinoma (ESCC). This retrospective analysis was conducted with 391 patients with ESCC who underwent radical CCRT with induction or CCT or CCRT only from January 2016 to October 2020 at the Fourth Hospital of Hebei Medical University in Shijiazhuang, Hebei province, China. Propensity score matching (PSM) analyses were performed. The primary outcome measure was efficacy included overall survival (OS) and progression-free survival (PFS). The final follow-up date ended on 31 May 2024. It showed a significantly better survival curve for OS in the CCRT + CCT group than the CCRT group (P=0.02, χ2=5.503). It showed a significantly better survival curve for PFS in the CCRT + CCT group than the CCRT group (P=0.002, χ2=9.788). It showed a significantly better survival curve for OS in the CCRT + CCT group than the ICT + CCRT group (P=0.046, χ2=3.986). It showed a significantly better survival curve for PFS in the CCRT + CCT group than the ICT + CCRT group (P=0.01, χ2=6.610). No significant differences were showed in treatment-related adverse events. Lesion length, N-staging, and combination of radiotherapy and chemotherapy were the independent prognostic factors for OS and PFS. For inoperable ESCC patients, CCRT + CCT showed the best OS and PFS rates than ICT + CCRT and CCRT. There were no significant differences in treatment-related adverse events. Lesion length, N-staging, and combination of radiotherapy and chemotherapy were the independent prognostic factors for OS and PFS.

High versus standard radiation dose of definitive chemoradiotherapy combined with immunotherapy for inoperable esophageal squamous cell carcinoma: A multicenter propensity score matching analysis.

e16118 Background: There is no consensus of the radiation dose for esophageal squamous cell carcinoma (ESCC) in the setting of definitive chemoradiotherapy (dCRT) combined with immunotherapy. This study aimed to compare the efficacy and safety of high-dose (HD) versus standard-dose radiotherapy (SD) for locally inoperable ESCC. Methods: Patients with locally advanced unresectable ESCC or advanced ESCC with supraclavicular lymph node metastases only who received high-dose (≥ 60Gy) or standard-dose (50-50.4Gy) radiation in dCRT combined with anti-PD-1 antibody as the first-line treatment from four academic cancer centers were enrolled. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. Results: Between March 2019 and July 2022, 328 patients were enrolled from four cancer centers in China, with 163 patients in the HD and 165 patients in the SD groups, respectively. The median follow-up time in the HD and SD groups were 28.9 and 25.9 months, respectively. There was no significant difference in overall survival (OS) (median OS: not reached in both, P = 0.080), progression-free survival (PFS) (median PFS: not reached vs. 30.3 months, P = 0.073), locoregional progression-free survival (LRPFS) and distant metastasis survival (DM) between the HD and SD groups. After 1:2 PSM, 156 patients in the HD and 78 patients in the SD groups were selected for further analyses. The results remained consistent and showed that the HD group had no significant benefits in OS (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.50-1.51, P = 0.624), PFS (HR = 0.79, 95%CI = 0.51-1.23, P = 0.300), LRPFS (HR = 0.75, 95%CI = 0.47-1.19, P = 0.228) and DM (HR = 1.05, 95%CI = 0.64-1.73, P = 0.849), compared with the SD group. In terms of failure patterns, the incidences of locoregional failure only (13.5% vs. 16.7%, P = 0.512), distant failure only (10.9% vs. 9.0%, P = 0.648) and synchronous locoregional and distant failure (2.6% vs. 6.4%, P = 0.164) were similar between two groups. No significant difference was found in the incidences of hematological toxicities, esophagitis, pneumonia (12.2% vs. 10.3%, P = 0.664) and fistula (7.1% vs 9.0%, P = 0.603) between the HD and SD groups. Conclusions: Compared with a radiation dose of 50-50.4Gy, the increase in radiation dose (≥60Gy) did not result in survival benefits for inoperable ESCC patients receiving dCRT combined with immunotherapy. Furthermore, similar failure patterns and toxicities were observed between the two treatment groups.

Effect of nivolumab combined with definitive chemoradiotherapy on response rate for esophageal cancer: An immune active intrinsic subtype could be its biomarker—The NOBEL trial.

4068 Background: The usefulness of combined therapy with immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) and its potential biomarker of treatment efficacy for esophageal cancer remains unclear. We investigated the safety, efficacy, and associated biomarkers of combined therapy with ICI and definitive CRT in operable and inoperable esophageal squamous cell carcinoma (ESCC). Methods: This prospective single-arm phase 2 trial was performed at five hospitals in Japan. Patients aged 20–75 years with histologically confirmed ESCC, an ECOG PS score of 0 or 1, and adequate organ and bone marrow functions were eligible. Inoperable patients did not have distant organ metastasis. Patients did not receive any chemotherapy or surgical resection as an initial therapy. Concurrent radiotherapy (50.4 Gy/28 fractions to the primary lesion and 41.4 Gy/23 fractions to the regional LN area) consisted of 4 courses of CF (cisplatin, 75 mg/m2/day, day 1; 5-fluorouracil, 1000 mg/m2/day, days 1–4) plus nivolumab (240 mg/m2/day, every 2 weeks for up to 1 year). The primary endpoint was safety. The incidence rates of nonhematological toxicity grade ≥ 4 and pneumonitis grade ≥ 3 were ≤10% and ≤15%, respectively. The secondary endpoints included overall survival (OS), progression-free survival (PFS), complete response (CR) rate, and time to esophagectomy-free survival (EFS). Sixty patients were to be accrued, but the trial enrollment was terminated because of slow accrual. This trial was registered as jRCT1091220408. Results: Between January 2019 and September 2021, 42 patients were enrolled. Twenty-five patients had operable disease and 16 had inoperable disease. Two patients (4.8%) experienced grade 3 pneumonitis, suggesting that the primary endpoint was met. The median relative dose intensity of nivolumab was 92.4%. One-year OS, PFS, and EFS rates in all cases were 92.7%, 65.4%, and 78.0%, respectively. One-year OS, PFS, and EFS rates in operable and inoperable cases were 100%, 79.6%, and 84.0% and 81.3%, 43.8%, and 68.8%, respectively. The CR and objective response rates were 73.2% (95% confidence interval [CI]: 58.1%–84.3%) and 87.8% (95% CI: 74.5%–94.7%), respectively. The CR rates in operable and inoperable cases were 84% (95% CI: 65.3%–93.6%) and 56.3% (95% CI: 33.2%–76.9%), respectively. Immune high-active intrinsic subtype before treatment (n=4) with an expression score > 80 of 51 immune-related genes showed a high CR rate (100%, n=4), whereas the immune low-active intrinsic subtype (n=37) with an expression score < 80 showed a relatively high CR rate (70%). Conclusions: Nivolumab combined with definitive CRT provided encouraging efficacy and acceptable toxicity in patients with ESCC. Immune high-active intrinsic subtype before treatment has the potential to predict a high CR rate for this combination treatment. Clinical trial information: jRCT1091220408 .

Efficacy of Oesophageal self expandable metal stent placement for palliation of dysphagia in inoperable oesophageal cancer patients: A low-income country perspective

Efficacy of Oesophageal self expandable metal stent placement for palliation of dysphagia in inoperable oesophageal cancer patients: A low-income country perspective

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial

BackgroundDefinitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC.MethodsThis is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints.DiscussionThis study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC.Trial registrationChiCTR1800017646.

Comparative Effectiveness of Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiotherapy for Patients With Inoperable Esophageal Squamous Cell Carcinoma Undergoing Curative-Intent Concurrent Chemoradiotherapy

IntroductionThis study compared outcomes in patients with inoperable esophageal squamous cell carcinoma (ESCC) undergoing curative-intent concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) versus intensity-modulated proton therapy (IMPT). MethodsThe study encompassed a retrospective cohort analysis of patients with inoperable ESCC who underwent curative-intent CCRT from January 1, 2015, to December 31, 2020, with data sourced from the Taiwan Cancer Registry Database. In this study, both IMRT and IMPT delivered a total equivalent effective dose of approximately 5040 cGy in 28 fractions, accompanied by platinum-based chemotherapy administered as per established protocols. Multivariate Cox regression analyses were performed to assess oncologic outcomes, and statistical analyses were conducted, including inverse probability of treatment-weighted and Fine and Gray method for competing risks. ResultsThe observed risks of ESCC-specific and all-cause mortality were lower in patients treated with IMPT compared with those treated with IMRT, with adjusted hazard ratios (aHRs) of 0.62 (95% confidence interval [CI]: 0.58–0.70) and 0.72 (95% CI: 0.66–0.80), respectively. IMPT also reduced grade 2 radiation-induced side effects, such as pneumonitis, fatigue, and major adverse cardiovascular events, with aHRs (95% CI) of 0.76 (0.66–0.82), 0.10 (0.07–0.14), and 0.70 (0.67–0.73), respectively. However, IMPT was associated with an increased risk of grade 2 radiation dermatitis, with aHR (95% CI) of 1.48 (1.36–1.60). No substantial differences were found in the incidence of radiation esophagitis between IMPT and IMRT when adjusting for covariates. ConclusionIMPT seems to be associated with superiority over IMRT in managing patients with inoperable ESCC undergoing curative-intent CCRT, suggesting improved survival outcomes and reduced toxicity. These findings have significant implications for the treatment of ESCC, particularly when surgery is not an option.

CT-Based Radiomics Combined with Genomics may Predict Survival in Esophageal Cancer Patients Receiving Definitive Chemoradiotherapy.

Definitive chemoradiotherapy (dCRT) is a standard treatment option for locally advanced stage inoperable esophageal squamous cell carcinoma (ESCC). Evaluating clinical outcome prior to dCRT remains challenging. The purpose of this study was to evaluate the predictive power of contrast-enhanced computed tomography (CT)-based radiomics in combination with genomics for the treatment efficacy of ESCC patients after dCRT. A total of 118 ESCC patients who received dCRT were enrolled in this retrospective study. These patients were randomly divided into the training group (N = 82) or the validation group (N = 36). Radiomic features were derived from the region of primary tumor on pretreatment CT images, also known as the region of interest (ROI), and clinical features were generated from medical records. The least absolute shrinkage and selection operator (LASSO) regression was conducted to select optimal radiomic features, and Rad-score was calculated to predict progression-free survival (PFS) in the training group. Genomic DNA was extracted from formalin-fixed and paraffin-embedded pre-treatment biopsy tissue. The univariate and multivariate COX analyses were undertaken to determine the predictors for developing models. The area under receiver operating characteristic curve (AUC) and the C-index were used to evaluate the predicting performance and the discriminating ability of prediction models, respectively. A total of 851 radiomic features were extracted from each CT image. The final Rad-score were constructed from 6 radiomic features to predict PFS. Multivariate analysis demonstrated that Rad-score and HRR pathway alterations were independent prognostic factors correlated with PFS. The C-index of integration model in combination with radiomics and genomics was better than that of radiomics or genomics model in the training group (0.616 vs 0.587 or 0.557) and the validation group (0.649 vs 0.625 or 0.586). Kaplan-Meier survival analysis also showed significant differences between different risk subgroups in the training and validation groups. The Rad-score based on pre-treatment CT and HRR pathway alterations could predict PFS for patients with ESCC after dCRT, with better predictive efficacy of combined radiomics and genomics models.

Effectiveness of S-1–Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma

Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for patients with inoperable esophageal cancer. However, patients tend to tolerate intravenous chemotherapy less well with age and comorbidities. It is essential to find a better treatment modality that improves survival outcomes without reducing the quality of life. To evaluate the effectiveness of simultaneous integrated boost radiotherapy (SIB-RT) with concurrent and consolidated oral S-1 chemotherapy for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma (ESCC). This multicenter, phase III randomized clinical trial was conducted between March 2017 and April 2020 in 10 centers in China. Patients with inoperable, locally advanced, clinical stage II to IV ESCC were enrolled and randomized to receive SIB-RT concurrent with and followed by oral S-1 chemotherapy (CRTCT group) or SIB-RT alone (RT group). Data analysis was completed on March 22, 2022. In both groups, the planning gross tumor volume was administered with radiation dose of 59.92 Gy and the planning target volume was administered with radiation dose of 50.4 Gy, in 28 fractions each. In the CRTCT group, concurrent S-1 was administered on radiotherapy days, and consolidated S-1 was administered at 4 to 8 weeks after SIB-RT. The primary end point was overall survival (OS) of the intent-to-treat population. Secondary end points were progression-free survival (PFS) and toxicity profile. A total of 330 patients (median [IQR] age, 75.5 [72-79] years; 220 [66.7%] male patients) were included, with 146 patients randomized to the RT group and 184 randomized to the CRTCT group. A total of 107 patients (73.3%) in the RT group and 121 patients (67.9%) in the CRTCT group were clinically diagnosed with stage III to IV disease. At the time of analysis of the 330 patients in the intent-to treat-population (March 22, 2022), OS was improved in the CRTCT group compared with the RT group at 1 year (72.2% vs 62.3%) and 3 years (46.2% vs 33.9%; log-rank P = .02). PFS was similarly improved in the CRTCT group compared with the RT group at 1 year (60.8% vs 49.3%) and 3 years (37.3% vs 27.9%; log-rank P = .04). There was no significant difference in the incidence of treatment-related toxic effects higher than grade 3 between the 2 groups. Grade 5 toxic effects occurred in each group, including 1 patient who experienced myelosuppression and 4 patients with pneumonitis in the RT group and 3 patients with pneumonitis and 2 patients with fever in the CRTCT group. These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable ESCC, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone. ClinicalTrials.gov Identifier: NCT02979691.

Quality of life and survival outcomes of patients with inoperable esophageal squamous cell carcinoma after definitive radiation therapy: A multicenter retrospective observational study in China from 2015 to 2016

ObjectivesTo investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. MethodsIn this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon–Mann–Whitney test. Overall survival (OS) was estimated using the Kaplan–Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. ResultsThe data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70–3.47]; P < 0.001) or three-dimensional radiotherapy (3DRT; HR, 1.45 [95% CI, 1.14–1.84]; P = 0.003) had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO. Of the 716 (23.4%) long-term survivors who completed the HRQL questionnaire, nearly 70% patients were still able to swallow normally or almost normally, and >80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. ConclusionsThis large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Model integrating CT-based radiomics and genomics for survival prediction in esophageal cancer patients receiving definitive chemoradiotherapy

BackgroundDefinitive chemoradiotherapy (dCRT) is a standard treatment option for locally advanced stage inoperable esophageal squamous cell carcinoma (ESCC). Evaluating clinical outcome prior to dCRT remains challenging. This study aimed to investigate the predictive power of computed tomography (CT)-based radiomics combined with genomics for the treatment efficacy of dCRT in ESCC patients.MethodsThis retrospective study included 118 ESCC patients who received dCRT. These patients were randomly divided into training (n = 82) and validation (n = 36) groups. Radiomic features were derived from the region of the primary tumor on CT images. Least absolute shrinkage and selection operator (LASSO) regression was conducted to select optimal radiomic features, and Rad-score was calculated to predict progression-free survival (PFS) in training group. Genomic DNA was extracted from formalin-fixed and paraffin-embedded pre-treatment biopsy tissue. Univariate and multivariate Cox analyses were undertaken to identify predictors of survival for model development. The area under the receiver operating characteristic curve (AUC) and C-index were used to evaluate the predictive performance and discriminatory ability of the prediction models, respectively.ResultsThe Rad-score was constructed from six radiomic features to predict PFS. Multivariate analysis demonstrated that the Rad-score and homologous recombination repair (HRR) pathway alterations were independent prognostic factors correlating with PFS. The C-index for the integrated model combining radiomics and genomics was better than that of the radiomics or genomics models in the training group (0.616 vs. 0.587 or 0.557) and the validation group (0.649 vs. 0.625 or 0.586).ConclusionThe Rad-score and HRR pathway alterations could predict PFS after dCRT for patients with ESCC, with the combined radiomics and genomics model demonstrating the best predictive efficacy.

Endoscopic debulking resection with additive chemoradiotherapy: Optimal management of advanced inoperable esophageal squamous cell carcinoma.

BACKGROUNDThere is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) who are not eligible to undergo surgical treatment.AIMTo introduce a novel therapy called endoscopic debulking resection (EdR) followed by additive chemoradiotherapy (CRT) and evaluate its efficacy and safety.METHODSAdvanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received EdR followed by CRT were deemed the EdR + CRT group and those without CRT were deemed the EdR group. Overall survival (OS), progression-free survival (PFS), and adverse events were evaluated.RESULTSA total of 41 patients were enrolled. At a median follow-up of 36 mo (range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent EdR plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent EdR alone (1-year OS, 83.3%; 2-year OS, 58.3%; 3-year OS, 50%; P = 0.05). The estimated 2-year cumulative PFS rate after EdR + CRT was 85.7%, while it was 61.5% after EdR (P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage (stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the EdR procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after EdR.CONCLUSIONEdR plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.

A PROSPECTIVE AND COMPARATIVE STUDY ON CONCURRENT RADIOTHERAPY WITH GEFITINIB VERSUS RADIOTHERAPY ALONE IN THE TREATMENT OF ELDERLY PATIENTS WITH CARCINOMA OESOPHAGUS

Objective: Concurrent chemoradiotherapy (CTRT) is the primary treatment for inoperable carcinoma esophagus. However, elderly patients are often not capable of tolerating CTRT, leaving radiotherapy as only option available for them. Many studies showed efficacy of anti-EGFR agent Gefitinib with acceptable toxicity profile in carcinoma esophagus patients. Hence, in this study, we compared radiation along with Gefitinib against radiation alone for the treatment of inoperable esophageal carcinoma in elderly patients in terms of locoregional control and toxicity profile. Methods: Patients of 50–70 years age group with inoperable squamous cell carcinoma esophagus were randomized in two groups – the control group received external beam radiotherapy 50.4 Gy in two phases over 5 weeks and the study group received radiotherapy with same dose along with Tab Gefitinib-250 mg daily during the radiotherapy. Response assessment was done after completion of treatment and all patients were followed up weekly during the course of treatment and then at every month for at least 6 months. Results: Overall response rate (complete+partial response) was better in study arm (80% vs. 70%), but not statistically significant (p=0.221). Just after treatment completion dysphagia of grade2 and above was more in control arm but after 3 months there was rise in incidences of dysphagia in study arm (66.6% vs. 60% p=0.632). Although statistically not significant, gefitinib containing study arm showed more incidences of higher grade of diarrhoea (20% vs. 15%, p=0.843) and moderate to severe grade of anaemia (90% vs. 66%, p=0.921). Conclusion: We can say that concomitant treatment with Gefitinib and radiotherapy was well tolerated and effective in elderly patients of inoperable carcinoma esophagus.

645 THE OUTCOMES OF PALLIATIVE SELF-EXPANDING METALLIC SEM) STENTS IN THE MANAGEMENT OF INOPERABLE ESOPHAGEAL CARCINOMA.

Abstract The incidence of esophageal carcinoma (EC) in Singapore is declining since 1970s. However, the age-incidence curve in 2010s shows a steep rise after age 40-50s. The majority of EC patients presented late with locally advanced or metastatic disease. The outcomes of inoperable esophageal carcinoma treated with palliative self-expanding metallic (SEM) stents were reviewed. Methods Consecutive cases of EC including Siewert Type I adenocarcinoma of esophago-gastric junction (AEG) were identified from electronic medical records from August 2015 to February 2021. There were 78 cases of EC and of which 14 were stented. The outcomes of inoperable or metastatic EC cases treated with palliative SEM stents were analyzed. Other palliative treatment included best supportive care and palliative chemotherapy with or without radiotherapy. Results The demographics showed the mean age of 73 ± 11 years with ECOG score 0-1 in 86% and mean BMI 19.1 ± 3.8. All were males with the risks from smoking in 85% and alcohol in 50%. The mean length of EC was 6.2 ± 2.6 cm. There were 10 Wallflex and 4 Ultraflex partially covered stents deployed successfully. The pre-stent dysphagia score was 3 in 72% and 4 in 29% whilst all had post-stent score of 1. The mean duration of survival was 4.4 ± 4.1 months. Post-stent complications included stent migration without obstruction and food bolus obstruction. Conclusion About 18% of patients diagnosed with advanced symptomatic EC were treated with palliative SEM stent insertion in a safe and effective manner. Those at risk were elderly males with smoking history. All stented cases had immediate improvement of dysphagia score and were able to tolerate soft diet. The overall duration of survival was variable up to 1 year likely due to different tumour biology and concurrent palliative systemic therapy.

A single-institution phase I feasibility study of dose-escalated IMRT for non-operative locally advanced esophageal carcinoma

Background and purposeRadiation dose escalation to improve poor outcomes with chemoradiation in locally advanced esophageal carcinoma is limited in part by increased toxicity. This Phase I study investigates the use of IMRT to improve tolerability of dose escalation. Materials and methodsA single-institution, prospective study was conducted between 2007 and 2013 for individuals with inoperable esophageal carcinoma. Gross disease received 60 Gy in 30 fractions and at-risk sites received 54 Gy with simultaneous integrated boost. Concurrent chemotherapy primarily consisted of cisplatin/5-FU. The primary objective was to assess feasibility (<15% rate of grade 4–5 toxicity). Secondary objectives included assessment of overall survival (OS), progression free survival (PFS), and locoregional (LRR) and distant recurrence. ResultsTwenty-six patients were enrolled with median follow up of 17.6 months (range 0.1 to 152.0). The majority were AJCC 7th edition Stage III (54%), distal esophagus primary (81%), and adenocarcinoma histology (85%). Twenty-one patients (81%) completed their course of radiation therapy, while only 55% received 2 cycles of concurrent cisplatin/5-FU. One grade 5 and one grade 4 cardiac event occurred, both during chemoradiation and before receiving 50 Gy. The 3-year OS was 48.6% (95% CI: 32.5 to 72.2%) and PFS was 28.5% (95% CI: 14.6 to 55.5%). Half developed distant failure with LRR occurring in 10 patients (38%), isolated in 5 patients. ConclusionWhile feasibility was demonstrated, toxicity and compliance remained limiting factors with outcomes similar to historical controls. There remains an uncertain role for dose escalation in definitive management of locally advanced esophageal cancer.

Immediate Results of Concurrent Chemoradiotherapy with Inoperable Esophageal Squamous Cell Carcinoma

Background: The incidence of esophageal cancer is increasing. In this connection, the search for the most effective methods of treating this disease continues. In most patients, esophageal cancer is diagnosed at III– IV stages of the disease. Currently, the standard of treatment for inoperable patients is chemo radiotherapy. Brachytherapy is one of the perspective methods of radiation therapy. Using of brachytherapy in the complex treatment of patients with esophageal cancer makes possible to increase the radiation dose without increasing the risk of complications after treatment.Methods: The study included 20 patients with inoperable esophageal cancer (most of them with III stages, 60 %). The age of the patients is from 51 to 89 years, ECOG performance status ½ (25 %/75 %), dysphagia score 1/2/3–4 (25 %,50 %, 25 %). All patients were diagnosed with esophageal squamous cell carcinoma. Most patients were with tumor in the middle third of the esophagus (70 %). The greatest length of the tumor was 10 cm. On the first stage of treatment patients underwent external-beam radiation therapy 46 Gy in 2 Gy fractions with simultaneous chemotherapy. After that, brachytherapy was performed (single dose of 5 Gy, 2 fractions with an interval of 6–7 days, 62,8 Gy (EQD2, α/β = 10 Gy).Results: Patients received therapy support for cardiovascular and lung diseases and nutritional support before, during and following chemoradiotherapy. There were no patients with hematological toxicity grade 3–4. Esophagitis grade 2 was noted in 40 % of patients, grade 1 in 60 % of patients. Esophagitis resolved on its own 2 weeks after completion of therapy. Complete tumor regression was observed in 10 % of patients, partial regression in 80 % of patients, stabilization of tumor process was observed in 10 % of patients. All patients have a poor QOL due to physical and psychological disorders. The general health situation and physical function after 3 months of treatment was improved compared to the prior to treatment period.

Docetaxel and nedaplatin twice a week with concurrent definitive radiotherapy in inoperable esophageal squamous cell carcinoma: A phase I trial (GASTO-1021)

PurposeThis phase I trial aimed to determine the maximal tolerated dose (MTD) of incorporating a twice-weekly docetaxel and nedaplatin regimen into definitive concurrent chemoradiotherapy (CCRT) as radiosensitizers in patients with inoperable esophageal squamous cell carcinoma (ESCC). MethodsThe CCRT regimen included docetaxel (5 mg/m2, 10 mg/m2, or 15 mg/m2) and nedaplatin (5 mg/m2, 10 mg/m2, or 15 mg/m2) twice-weekly based on the traditional 3 + 3 dose escalation strategy, and radiotherapy (64 Gy in 32 fractions). The primary goals were to determine the MTD of concurrent chemotherapy and the dose limiting toxicities (DLTs). In-field objective response rate (ORR) was investigated. ResultsFifteen patients had been recruited and analyzed. DLT involving persistent grade 3 esophagitis over 1 week was observed in all three patients (3/3) at dose level 3 (15 mg/m2), and two patients (2/6) experienced DLTs in the dose level 2 (10 mg/m2) due to esophageal fistula and persistent grade 3 esophagitis over 1 week, while one patient (1/6) treated at dose level 1 (5 mg/m2) exhibited DLT owing to Grade 3 increased liver enzymes, suggesting a MTD of 5 mg/m2. The in-filed ORR was both 100% in all patients and those receiving MTD. The 1-year loco-regional recurrence-free survival rate was 83.3%, 83.3% and 66.7% in dose level 1, 2, and 3, respectively. ConclusionsThe MTD of twice-weekly docetaxel and nedaplatin regimen was 5 mg/m2 in inoperable ESCC patients treated with definitive CCRT. Low dose concurrent docetaxel and nedaplatin showed promising radiosensitizing effect on in-filed disease control and good tolerability.

A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Confirmation of the prognostic value of pretherapeutic tumor SUR and MTV in patients with esophageal squamous cell carcinoma.

The prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. In a recent publication, we were able to show that PET can provide independent prognostic information in such a patient group and that the tumor-to-blood standard uptake ratio (SUR) can improve the prognostic value of tracer uptake values. The present investigation addresses the question of whether the distinctly improved prognostic value of SUR can be confirmed in a similar patient group that was examined and treated at a different site. 18F-FDG PET/CT was performed in 147 consecutive patients (115 male, 32 female, mean age: 62 years) with newly diagnosed esophageal squamous cell carcinoma prior to definitive radiochemotherapy. In the PET images, the metabolic active volume (MTV) of the primary tumor was delineated with an adaptive threshold method. For the resulting ROIs, SUVmax and total lesion glycolysis (TLG = MTV × SUVmean) were computed. The blood SUV was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as ratio of tumor SUV and blood SUV. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant-metastases-free survival (DM), and locoregional control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. Univariate Cox regression revealed MTV, TLG, and SURmax as significant prognostic factors for OS. MTV as well as TLG were significant prognostic factors for LRC while SURmax showed only a trend for significance. None of the PET parameters was prognostic for DM. In univariate analysis, SUVmax was not prognostic for any of the investigated clinical endpoints. In multivariate analysis (T-stage, N-stage, MTV, and SURmax), MTV was an independent prognostic factor for OS and showed a trend for significance for LRC. SURmax was not an independent predictor for OS or LRC. When including the PET parameters separately in multivariate analysis, MTV as well as SURmax were prognostic factors for OS indicating that SURmax is independent from the clinical parameters but not from MTV. In addition, MTV was an independent prognostic factor for LRC in this separate analysis. Our study revealed a clearly improved prognostic value of tumor SUR compared to tumor SUV and confirms our previously published findings regarding OS. Furthermore, SUR delivers prognostic information beyond that provided by the clinical parameters alone, but does not add prognostic information beyond that provided by MTV in this patient group. Therefore, our results suggest that pretherapeutic MTV is the parameter of choice for PET-based risk stratification in the considered setting but further investigations are necessary to demonstrate that this suggestion is correct.

Comparative analysis between induction chemotherapy combined with concurrent chemoradiotherapy and chemoradiotherapy alone for thoracic esophageal squamous cell carcinoma

Objective To compare the clinical efficacy and safety between induction chemotherapy (IC) followed by concurrent chemotherapy (CRT) and CRT alone in patients with inoperable thoracic esophageal squamous cell carcinoma (ESCC). Methods Between 2002 and 2015, clinical data of 267 thoracic ESCC patients undergoing definitive CRT based on docetaxel combined with cisplatin were retrospectively analyzed. Through a matched case-control study, 85 patients receiving IC combined with CRT were matched to those undergoing CRT alone at a ratio of 1vs.1, according to age, gender, performance status, tumor location, tumor length, and TNM staging as the matching factors. Clinical efficacy and safety between two groups were statistically compared. Kaplan-Meier survival analysis was used to analyze the survival. The log-rank test was adopted to examine within-group differences. The Cox regression model was used for multivariate analysis. Results The median follow-up time for 170 patients was 18 months (range, 3-72 months). The overall objective response rates in the IC and CRT groups were 74.1% and 58.8%(P=0.035). The 3-year overall survival (OS) and progress-free survival (PFS) rates in the IC group were 44.2% and 34.8%, significantly higher than 29.7% and 15.4% in the CRT group (P=0.028, P=0.015). Subgroup analysis revealed that patients responsive to IC obtained significantly better OS (P=0.002), PFS (P=0.001), and local recurrence-free survival (LRFS)(P=0.002) compared with the IC non-responder, whereas the distant metastasis-free survival (DMFS) did not significantly differ (P=0.166). The incidence rate of grade 3–4 leukopenia in the IC group was significantly higher than that in the CRT group (38.8% vs. 24.7%, P=0.048). Multivariate analysis revealed that age and the addition of IC were independent prognostic factors for OS (P=0.003, 0.016). Conclusions Compared with concurrent CRT, IC in combination with CRT can yield better short-term efficacy and longer survival for ESCC patients. The risk of hematological toxicity in the IC group is relatively higher but tolerable. Prospective randomized trials are required to confirm the clinical efficacy and safety of IC for thoracic ESCC patients. Key words: Esophageal neoplasms/concurrent chemoradiotherapy; Induction chemotherapy; Prognosis

Palliative treatment with radiotherapy in patients of advanced esophageal carcinoma

Background: Esophageal carcinoma is high prevalence in Asia, including India and most of the patients present in advanced and inoperable stage. Most of the patients have poor nutritional status and low performance status. These patients are unable to tolerate radical treatment. Prognosis of these patients is very poor. There are no enough data of prospective study in palliation of dysphagia of the patients with inoperable esophageal carcinoma with radiotherapy in Eastern India. Objectives: The main objective of our study was palliation of dysphagia of the patients with inoperable esophageal carcinoma with radiotherapy. Materials and Methods: The study was done with 43 patients with histopathologically proven squamous cell carcinoma and/or adenocarcinoma at thoracic esophagus, intraluminal brachytherapy feasible. Patients were received external beam radiotherapy palliative dose 30 Gy in 10 fractions for 2 weeks followed by intraluminal high-dose rate brachytherapy 6 Gy per fraction per week for 2 weeks. Results: In our study, the mean age of the patients was 58 years (age range 48 years–70 years). 1 month after completion of intraluminal brachytherapy, a number of patients with improvement of dysphagia were 34 (79%). The improvement of dysphagia was maintained 25 (73.5%) patients at 3-month completion of treatment and 14 (56%) patients at 6-month completion of treatment. The median duration of dysphagia relief was 5.2 months. Post-radiotherapy complications as chest pain were seen in 10 (23.2%) patients, esophageal strictures were developed in 7 (16.3%) patients, ulcerations were in 4 (9.3%) patients, and esophageal fistula was developed in 1 (2.3%) patient. Conclusion: The patients with advanced inoperable or metastatic esophageal carcinoma and poor performance status, palliative radiotherapy are effective modality of treatment for the improvement of dysphagia.