Unresectable Esophageal Carcinoma Research Articles

Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis.

To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach. A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs). The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders. The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.

291. CLINICAL OUTCOMES OF IMMUNOCHEMOTHERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL SQUAMOUS CELL CARCIONOMA

Abstract Background/Aim KEYNOTE-590 and CheckMate 648 study showed significantly feasible clinical outcomes in patients with advanced esophageal carcinoma. Herein, we report our clinical results of immunochemotherapy for unresectable and recurrent esophageal squamous cell carcinoma. Patients and Methods 17 patients who received pembrolizumab plus 5-fluorouracil and cisplatin (IO+C) and 9 patients who received nivolumab plus ipilimumab (IO+IO) were enrolled. Results The median age of the IO+C group was 70 years, and all patients had unresectable disease. A median of 2 courses of treatment were performed, and the best overall response rate was 68.6% including CR in 2 patients, PR in 9 patients, SD in 4 patients, PD in 1 patient and NE in 1 patient. One-year progression-free survival rate (PFS) was 36.1% and one-year overall survival (OS) was 64.6%. Immune-related adverse events (irAE) included liver damage in 4 patients, skin damage in 4 patients, thyroid dysfunction in 2 patients and lung damage in 1 patient. The median age of the IO+IO group was 79 years, with 3 patients of unresectable disease and 6 patients of recurrence. A median of 2 courses of treatment were performed, and the best overall response rate was 71.4% including CR in 4 patients, PR in 1 patient, SD in 1 patient, PD in 1 patient, and NE in 2 patients. One-year PFS was 68.6% and one-year OS was 85.7%. irAE included liver damage in 3 patients, skin damage in 6 patients, thyroid dysfunction in 2 patients, rhabdomyolysis in 1 patient and hypopituitarism in 1 patient. Discussion/Conclusion Currently, in our institute, IO+C is the first choice for unresectable esophageal carcinoma, and IO+IO is selected for patients who are unresponsive or intolerant to FP, patients requiring outpatient treatment and patients with recurrent disease. Although long-term clinical outcomes will need to be examined, immunochemotherapy is very useful and it is necessary to examine the effective use of IO+C and IO+IO in the future.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients: A prospective phase II study.

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002 (NRS-2002) score. Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control (LRC) rate. A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3 [95% confidence interval (95% CI), 31.4-35.1)] months. The LRC rate was 77.2% (95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival (OS) rate and event-free survival (EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio (HR)=0.16; 95% CI, 0.04-0.70; P=0.015], OS (HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS (HR=0.25; 95% CI, 0.08-0.75; P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred. For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Camrelizumab in combination with chemotherapy versus concurrent chemoradiotherapy for the conversion of locally advanced unresectable oesophageal squamous carcinoma: protocol for a two-arm, open-label phase II trial

IntroductionOesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour...

Survival benefit of combined immunotherapy and chemoradiotherapy in locally advanced unresectable esophageal cancer: an analysis based on the SEER database.

While simultaneous chemoradiotherapy remains the established therapeutic modality for patients afflicted with locally advanced esophageal cancer, the effectiveness of this radical approach falls short of the desired outcome. Numerous investigations have illuminated the prospect of enhancing therapeutic efficacy through the amalgamation of chemoradiotherapy and immunotherapeutic interventions. Consequently, we embarked on an examination to scrutinize the potential survival advantages conferred by the confluence of chemoradiotherapy and immunotherapy in relation to locally advanced unresectable esophageal carcinoma, drawing upon the extensive SEER database for our analysis. We extracted clinicopathological attributes and survival statistics of patients afflicted with locally advanced unresectable esophageal carcinoma, diagnosed within the temporal span encompassing the years 2004-2014 and 2019-2020, from the extensive SEER database. To discern disparities in both overall survival (OS) and cancer-specific survival (CSS) between the cohorts subjected to chemoradiotherapy combined with immunotherapy and chemoradiotherapy alone, we employed analytical tools such as Kaplan-Meier analysis, the Log-rank test, the Cox regression proportional risk model, and propensity-matched score (PSM) methodology. A total of 7,758 eligible patients were encompassed in this research, with 6,395 individuals having undergone chemoradiotherapy alone, while 1,363 patients received the combined treatment of chemoradiotherapy and immunotherapy. After 1:4 propensity score matching, 6,447 patients were successfully harmonized, yielding a well-balanced cohort. The Kaplan-Meier curves demonstrated a substantial enhancement in OS (P = 0.0091) and CSS (P < 0.001) for the group subjected to chemoradiotherapy combined with immunotherapy as compared to chemoradiotherapy alone. Further multivariable analysis with PSM confirmed that chemoradiotherapy combined with immunotherapy benefits OS(HR=0.89, 95% CI 0.81-0.98) and CSS (HR=0.68, 95% CI 0.61-0.76). In addition, Univariable and multivariable Cox regression analyses of the matched patient groups unveiled several independent prognostic factors for OS and CSS, including sex, age, marital status, tumor location, tumor size, pathologic grade, SEER historic staging, and treatment modality. Among these factors, being female, married, and receiving chemoradiotherapy combined with immunotherapy emerged as independent protective factors, while age exceeding 75 years, non-superior segment tumor location, tumor size greater than 6cm, Grade 3-4 pathology, and regional SEER historic staging were all found to be independent risk factors. The survival advantage of the chemoradiotherapy combined with the immunotherapy group over the chemoradiotherapy alone group was substantial. This investigation furnishes compelling evidence that the integration of immunotherapy with chemoradiotherapy confers a noteworthy survival advantage when contrasted with conventional chemoradiotherapy for individuals grappling with locally advanced unresectable esophageal carcinoma.

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.

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma—randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol

BackgroundIn case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67).MethodsARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory.The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging.Ancillary studies are plannedPD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers.ConclusionResults of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation.Trial registrationClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

Thoracoscopic esophageal drainage for tracheal compression due to mucocele after esophagogastric bypass: a case report

BackgroundEsophagogastric bypass is performed for esophageal strictures. Mucus retention, known as mucocele, sometimes occurs at the stricture oral side of the remnant esophagus. It is often asymptomatic and is expected to be naturally decompressed, but it may cause respiratory failure depending on the case. Herein, we report a case in which we successfully performed thoracoscopic esophageal drainage as emergency airway management due to tracheal compression by a mucocele after esophagogastric bypass for unresectable esophageal cancer with esophagobronchial fistula.Case presentationA 56-year-old man underwent esophageal bypass surgery for an unresectable esophageal carcinoma with an esophagobronchial fistula following chemotherapy and radiation therapy. Nine months after bypass surgery, he experienced severe dyspnea due to tracheal compression caused by mucus retention on the oral side of the esophageal tumor. We planned thoracoscopic surgery for mucus retention drainage through the right thoracic cavity to secure the airway as an emergency procedure under general anesthesia. Intubation can be performed safely by guiding bronchoscopy in the semi-supine position. Upper esophageal dilation was observed on the cranial side of the azygos arch. We dissected the mediastinal pleura of the upper thoracic esophagus and exposed its wall. A 12-Fr silicone drain was placed in the esophagus through the right chest wall and 120 ml of white fluid was aspirated. He was discharged 9 days after surgery without complications and resumed treatment with an immune checkpoint inhibitor 23 days after surgery. Thereafter, he continued chemotherapy for esophageal cancer, but died of tumor progression and lung metastasis 35 months after bypass surgery and 25 months after thoracoscopic surgery.ConclusionsThoracoscopic esophageal drainage could be performed safely as emergency airway management, shorten the period of discontinuance, and allow cancer treatment to be resumed promptly. We believe that this thoracoscopic procedure is an effective and less invasive method if the percutaneous approach is difficult.

Safety and efficacy analysis of chemoradiotherapy/radiotherapy combined with nimotuzumab for treating unresectable oesophageal squamous cell carcinoma in elderly patients: a retrospective analysis

ObjectiveTo investigate the safety and efficacy of chemoradiotherapy or radiotherapy combined with nimotuzumab in the treatment of unresectable oesophageal squamous cell carcinoma (ESCC) in elderly patients.MethodsThis study retrospectively analysed 54 cases of elderly patients (aged over 70 years) with unresectable ESCC in our centre between December 2016 and November 2019. The patients were treated with a radiation dose of 50–61.6 Gy (25–30 fractions) combined with nimotuzumab for targeted therapy with or without chemotherapy according to each patient’s condition. The patients were observed for quality of life, safety, side effects and survival before and after the treatment.ResultsAmong the 54 patients, 26 were treated with nimotuzumab combined with chemoradiotherapy and 28 were treated with nimotuzumab combined with radiotherapy. Toxicities were mainly oesophagitis (≥ Grade 2, 38.9%), myelosuppression (≥ Grade 3, 24.1%) and hypoproteinaemia (any grade, 94.4%). The rates of complete response, partial response, disease stability and disease progression were 11.1% (6/54), 81.5% (44/54), 3.7% (2/54) and 3.7% (2/54), respectively, and the overall objective response rate was 92.6% (50/54). The median follow-up time was 35.1 months, and the 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 61.1% (1 year OS) and 35.2% (2 year OS), 42.6% (1 year PFS) and 16.7% (2 year PFS), respectively. The median OS and PFS rates were 16.0 and 10.0 months, respectively.ConclusionNimotuzumab combined with chemoradiotherapy or radiotherapy was well tolerated in elderly patients with unresectable ESCC. This combination can achieve a good treatment response and enhance survival.

Tolerance and efficacy of dose escalation using IMRT combined with chemotherapy for unresectable esophageal carcinoma: Long-term results of 51 patients

PurposeThe optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). Materials and methodsAll consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. ResultsA total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54–66) and 48Gy (44.8–56) delivered in 30 (27–35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8–19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0–46.0) and 4.6% (0.7–19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3–31.3) with a median V40 of 3.3% (0.0–25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9–4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). ConclusionWe demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.

Radiotherapy progress in elderly patients with unresectable esophageal carcinoma

As the fourth leading cause of cancer death for years, esophageal carcinoma yields a high morbidity in China. In an aging society, the quantity of elderly patients with esophageal carcinoma is ever increasing. However, elderly patients have been excluded in most studies due to more comorbidities, lower performance status grade, worse therapeutic tolerance and other clinical features. Although clinical prognosis of esophageal carcinoma patients has been improved in the past decades, the clinical efficacy in the treatment of esophageal carcinoma in elderly patients is still unsatisfactory. Current options should be combined with novel therapeutic srategies to enhance the clinical efficacy. In this article, the clinical efficacy and adverse events of radiotherapy, radiochemotherapy, targeted therapy or immunotherapy in treating elderly patients with unresectable esophageal carcinoma were retrospectively analyzed. Key words: Esophageal neoplasm/radiotherapy; Elderly; Progress

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis

BackgroundSome Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma.MethodsThis study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival.ResultsIn this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group.ConclusionThe 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

A Phase 1/2 Radiation Dose Escalation Trial Using SIB-IMRT Technique With Concurrent Chemotherapy in Unresectable Esophageal Carcinoma

A Phase 1/2 Radiation Dose Escalation Trial Using SIB-IMRT Technique With Concurrent Chemotherapy in Unresectable Esophageal Carcinoma

Therapeutic evaluation between coventional fraction radiotherapy and intensity modulated radiation therapy combined with concurrent chemotherapy for esophageal carcinoma

Objective To evaluate the curative effect between conventional fraction radiotherapy (CFRT) and intensity modulated radiation therapy (IMRT) combined with concurrent chemotherapy for unresectable esophageal carcinoma. Methods 144 patients were enrolled into this study. They were divided into CFRT group and IMRT group. CFRT group (60 cases): irradiation field encompassed primary lesion and mediastinal lymph drainage regin. Neck and thoracic upper segment cases were made front thoraxT field irradiation first, DT 36 Gy/18 f, followed by two front oblique field made Iso-central irradiation, field width was 4.5-5.0 cm, gantry angle 50°-60°, wedge filter 30°, DT added to 66 Gy. For thorax middle or lower segment patients, field width was 6.0-6.5 cm, field length was that the tumor upper and lower each extended 3.0-5.0 cm, vertically irradiated in thoracic front and at the back, after DT 36 Gy/18 f, changed to two back ablique field, made Iso-central irradiation, DT added to 66 Gy. IMRT group (84 cases): GTV was esophageal primary lesion and metastasis lymph node (GTVnd); CTV included GTV, GTVnd and mediastinal lymph drainage region, at GTV around all was widened 0.8-1.0 cm, its upper and lower each extended 3.0-5.0 cm; PTV were in the basis of CTV, all were widened 0.5 cm again. With ≥95% isodose curve covering the PTV and the target dose was prescribed to PTV 60-64 Gy/30-32 f. Organ at risk (OAR): both lungs V20≤30%, spinal cord ≤45 Gy/6 weeks, heart V30≤40%. Chemotherapy of two groups was same, DDP 25-30 mg/m2 × 3-5 days, 5-Fu 450-500 mg/m2 × 5 days civ, 28 days were one period, total 2 period, after 1-3 months, strengthen chemotherapy 3-4 period. Results Leucopenia and radiation-induced esophagitis as shown by the WHO staging system were the most common acute toxicities, but were mainly grade 1 or 2. The incidence rate of leucopenia and radiation-induced esophagitis in CFRT group were 78.3% (47/60) and 83.3% (50/60), IMRT group were 82.1% (69/84) and 79.8% (67/84). After symptomatic treatment, all patients completed the planner treatment. During radiotherapy and after treatment, the patients showed grade 1-2 radiation-induced pneumonitis, CFRT group were 36.7% (22/60), but IMRT group were only 9.5% (8/84) (χ2= 9.99, P < 0.01). In CFRT group and IMRT group, the 1-, 3-, 5-year survival rates were 75.0% (45/60), 36.7% (22/60), 20.0% (17/84) and 79.8% (67/84), 35.7% (30/84), 21.4% (18/84), respectively. Conclusion The overall response and 5-year survival rates of CFRT and IMRT combined with concurrent chemotherapy are similar, however, the incidence of grade 1-2 radiation-induced pneumonitis of IMRT is low, which indicates that IMRT can reduce the lungs irradiational volume and dose. Key words: Esophageal neoplasms; Radiotherapy, intensity-modulated; Drug therapy; Radiation pneumonitis

90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: A pilot study.

359 Background: This prospective single-institution pilot study was undertaken to document the feasibility, safety, and efficacy of treatment of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. Methods: Between June 2010 and November 2012, 30 adult patients (22 men, 8 women; median age 61 years) with metastatic chemotherapy-refractory unresectable colorectal (n=15), neuroendocrine (n=9), biliary tract (n=3), pancreas (n=2), and esophageal (n=1) carcinomas underwent 45 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for 6 months after each treatment. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1. Time to maximum response, response duration, progression-free survival (hepatic and extrahepatic), and overall survival were measured. Results: Median target dose and activity were 111.6Gy and 2.5GBq per treatment session, respectively. All but 3 clinical AE were grade 1 or 2 in severity. The most frequent clinical AE were fatigue (83%), anorexia (50%), nausea (50%), abdominal pain (40%), vomiting (20%), fever (17%), and sweating (17%). Common metabolic and laboratory AE included hypoalbuminemia (50%), transaminitis (63%), and hyperbilirubinemia (27%). Serious AE included an unplanned hospital admission for carcinoid crisis, grade 3 vomiting, and grade 4 gastric ulcer. Patients with colorectal cancer had hepatic objective response rate (ORR) of 27% and a disease control rate (DCR) of 73%. Median progression-free and overall survival were 1.0 and 4.9 months, respectively. Patients with neuroendocrine tumors had hepatic ORR and DCR of 78% and 100%, respectively. Median progression-free survival was 18.5 months for this cohort. Conclusions: 90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort. Clinical trial information: NCT01290536.

Therapeutic p53 gene agent in the treatment of refractory cancer cases: A phase I study.

2543 Background: To evaluate the benefit of adding therapeutic p53 gene agent into the standard treatment regimens for refractory cancer cases. Methods: Recombinant adenoviral human p53 gene (rAd-p53), was given intravenously at a dose of 2×1012 viral particles /day on 5 consecutive days one week before routine anti-cancer treatment start, and was repeated after an interval of 16 days. The inclusion criteria include: 1.Pathologically confirmed recurrent cancers; 2. Disseminated cases; 3. Patients with key organ metastasis; 4.Unresectable lesions; 5.Chemo- or radio-therapy resistant cases. The exclusion criteria include: 1.With severe liver, kidney, heart or hemotologic disorders; 2.Pregnancy; 3.Without informed consent. Efficacy was evaluated according to the results of contrasted MRI or CT. Results: A total of 16 patients entered the study with a median age of 59 years old (range 30-76 years), 13 were male and 3 were female. 5 were recurrent cases(4 HNSCC and 1 esophageal cancer), 5 were widely infiltrated unresectable HNSCC, esophageal carcinoma(2 cases) and undifferentiated thyroid carcinoma(1 case). 3 were disseminated cases(2 NPC and 1 Lung cancer). Two cases were breast cancer with multiple brain metastasis. One was refractory central nervous lymphoma. One patient did not finish the planned chemoradiation due to radiation-induced pneumotitis. Another one patient experienced chemotherapy delay due to A grade 4 hemotologic toxicity. 93.8% patients had shivering and fever after injection of rAd-p53. Other acute toxicities during the treatment included: leukopenia(Grade 3/4) 43.8%, thrombocytopenia (Grade 3/4) 25.0%, oral mucositis(Grade 3/4) 18.8%, vomiting(Grade 2 and above) 31.3%, ALT elevation (Grade 2 and above) 6.3%. No Cr elevation was observed. The acute toxicities were controllable and reversible. At the 3 months after treatment, PR, SD and PD rate were 56.3%, 25.0% and 18.7%, respectively. Conclusions: The therapeutic p53 gene agent can be intravenously safely added to routine anti-cancer regimens with controllable and reversible acute toxicities. A randomized controlled phase II is needed to make clear the role of the therapeutic p53 gene agent.

Involved field irradiation compared with prophylactic nodal irradiation to unresectable esophageal carcinoma: A retrospective study.

e15180 Background: We retrospectively observed the failure patterns in patients of local advanced esophageal squamous cell carcinoma (ESCC) with involved field irradiation (IFI) or with intentional prophylactic nodal irradiation (PNI). Methods: The ESCC patients with unresectable lesion (length &gt;6 cm or T4 or obvious node metastasis) were retrospectively analyzed between 2003 and 2009. All the reviewed patients received 3D-CRT with cisplatin based chemotherapy. For the IFI cases, the GTV was defined as any visible esophageal lesion(GTVe) and clinical involved node(GTVn). The CTVe was defined as the GTVe plus a 3-4cm margin superior and inferior to the primary tumor and a 1.0 cm radial margin. CTVn was defined as the GTVn plus a 0.5cm radial margin. The PTV was defined as CTV plus a 1.0cm margin. For the PNI cases, the same margins outside the primary tumor as that in IFI, and the adjacent regional lymphatics was included in the CTV according to the different location of primary tumor. The prescribed dose to PTV in IFI group was 60-64 Gy in 6-7 weeks and to PNI group was 40-50GY in 4-5weeks followed by 10-20Gy to PTVe+n. Results: Thirty-six cases received IFI and 49 cases underwent PNI. There were no difference between IFI and PNI group in tumor length and nodal status. The clinical response rates were 94.4% and 97.9% in IFI and PNI group, respectively, and no statistical difference was found ( P=0.785).The patterns of first failure in IFI and PNI group were listed as follows:(1) involved field failure, 17/36 vs 34/49 , P=0.046; (2) prophylactic nodal failure, 10/36 vs 4/49 P=0.02; (3) out field of regional nodal failure, 8/36 vs 15/49 , P=0.464; (4) distant metastasis, 17/36 vs 26/49, P=0.663. The medium PFS were 8.5m vs 12.0m( P=0.602), and the median OS were 14.0m vs 16.0m ( P=0.924)in IFI and in PNI group, respectively, and no statistical difference was found. Conclusions: Chemo-radiotherapy with PNI for unresectable ESCC showed better prophylactic field control, but had no advantage over the IFI in LC, PFS and OS.The involved field failure and distant metastasis were the main causes of failure in both groups, which suggests that the prophylactic irradiation may be not necessary for this sub-group patients.

Temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma: is there an optimal time for stent removal?

To investigate the influence of the timing of stent removal on the outcome of temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma. Retrospective analysis was performed on 52 patients undergoing temporary stent placement. Stents were electively removed within 4 weeks in 15 patients (group A), 4-6 weeks in 17 patients (group B) and after 6 weeks in 20 patients (group C). Recurrent symptoms after stent removal, dysphagia score and overall survival periods were compared among the groups. Stent placement and removal were technically successful in all patients. The dysphagia score was significantly improved in all groups (P < 0.001). In 19 patients (36 %), recurrent symptoms occurred 15-441 days after stent removal. In group A, recurrent obstruction was significantly higher than in groups B (P = 0.049) and C (P = 0.019). Incidence of oesophago-respiratory fistulas in group C was significantly higher than in group A (P = 0.027). There was no significant difference in survival periods. The ideal time for stent removal likely falls between 4 and 6 weeks following the start of palliative CCRT allowing the temporary stents to relieve dysphagia effectively in patients with unresectable oesophageal carcinoma. • Stents are usually required for unresectable oesophageal carcinoma • Optimal timing of stent removal is 4-6 weeks after starting palliative CCRT. • Early stent removal (<4 weeks) is associated with higher recurrence rates. • Delayed stent removal (>6 weeks) is associated with greater oesophago-respiratory fistula development.

Double stents: airway stenting after esophageal-stent implantation for esophageal cancer.

Esophageal stenting with self-expandable metallic stents can effectively relieve malignant esophageal strictures in patients in whom chemoradiotherapy has failed. However, airway stenosis can sometimes occur after esophageal stenting. This study aims to evaluate the efficacy of double stents (combined esophageal and airway stents) in patients with recurrent and unresectable esophageal carcinoma in whom definitive chemoradiotherapy has failed. We retrospectively studied 35 patients who underwent esophageal stenting for recurrent esophageal carcinoma after failure of chemoradiotherapy. These patients were divided into 2 groups; the E group, consisting of patients who underwent esophageal stenting alone and the D group, consisting of patients who required airway stenting after esophageal stenting due to airway compression. Bronchoscopy was performed before esophageal stenting in all patients. In all 5 patients developed airway stenosis after esophageal stenting. With regard to the bronchoscopic findings before esophageal stenting, the incidence of category-2b findings was significantly higher in the D group than in the E group. Mean survival was 60 days (range 24-102 days). Accurate bronchoscopic examination with special attention to compression of the airway should be performed before esophageal stenting in patients in whom the bronchoscopic findings are classified as category 2b or higher.

Salvage endoscopic submucosal dissection for recurrent esophageal squamous-cell carcinoma after definitive chemoradiotherapy.

Although concurrent definitive chemoradiotherapy (CRT) is considered a standard treatment for unresectable esophageal carcinoma, CRT is associated with local failure (40-50%), and further interventions are needed in these cases. However, morbidity and mortality rates remain high among patients undergoing salvage esophagectomy for recurrent tumors. Here, we report a rare experience of salvage endoscopic submucosal dissection (ESD) for recurrent esophageal squamous-cell carcinoma (SCC) after definitive CRT. A 55-year-old male was diagnosed with unresectable advanced mid-thoracic esophageal SCC with lymph node metastases involving the trachea. After definitive CRT with cis-diamminedichloroplatinum (CDDP)/5-fluorouracil (5-FU) and 60Gy irradiation was performed, complete response was obtained. However, a recurrent esophageal SCC was detected in the mid-thoracic esophagus on endoscopy performed 6months after CRT. The tumor was resected en bloc using ESD without any complications. There was no recurrence for 4months after ESD. Salvage ESD may be a safe and effective treatment for recurrent esophageal SCC after CRT.