Unresectable Esophageal Cancer Research Articles

Recent updates in the therapeutic uses of Pembrolizumab: a brief narrative review.

Treatment of cancer has been improved with the discovery of biological drugs that act as immune checkpoint inhibitors. In 2017, FDA designated pembrolizumab, an immune checkpoint inhibitor employed in immunotherapy, as the first tissue-agnostic cancer treatment. To review pembrolizumab's use in oncology, gather and examine the latest discoveries regarding the effectiveness of pembrolizumab in cancer treatment. A literature review was conducted through PubMed(Medline) from January 2015 to December 2023 using "pembrolizumab", "cancer" and "treatment" as search terms. Pembrolizumab demonstrated effectiveness as primary treatment for metastatic nonsmall cell lung cancer, unresectable esophageal cancer, head and neck squamous cell carcinoma and alternative treatment for notable triple-negative breast cancer, biliary, colorectal, endometrial, renal cell, cervical carcinoma, and high microsatellite instability or mismatch repair deficiencies tumors. Pediatric applications include treatment for refractory Hodgkin lymphoma. Evolving research on pembrolizumab allows a deeper clinical understanding, despite challenges as variable patient responses. Pembrolizumab has emerged as a pivotal breakthrough in cancer treatment, improving patient outcomes and safety.

Prospective randomized comparative study between EBRT alone and EBRT with ILRT boost in locally advanced unresectable esophageal cancer - Tertiary rural Indian cancer center experience

Background: Local recurrence within the gross tumor volume following a conventional radiation dose of 50 Gy is a major hurdle in achieving a better prognosis for esophageal carcinoma. Consequently, there remains a lack of consensus globally regarding the optimal dose for definitive concurrent chemoradiotherapy. Certain studies propose that radiation dose escalation could enhance clinical outcomes. Aims and Objectives: The current study aimed to compare the safety and effectiveness of external beam radiotherapy (EBRT) alone versus EBRT with intraluminal radiotherapy (ILRT) boost. Materials and Methods: A total of 60 patients with locally advanced unresectable squamous cell carcinoma of the esophagus were prospectively enrolled in this study. A comparison was conducted between 50 Gy EBRT alone and 50 Gy EBRT with 8 Gy ILRT boost, alongside weekly concurrent chemotherapy, to assess the response and toxicities. Results: On initial assessment, a complete response (CR) was achieved in 76.66% of patients in the ILRT boost arm and 70% in the EBRT alone arm (P=0.559). At the 6th-month follow-up, 60% of patients in the ILRT boost arm and 50% in the EBRT alone arm still had a CR. No statistically significant differences were observed between the two arms in terms of leukopenia (P=0.576), nephrotoxicity (P=1.0), radiation dermatitis (P=0.615), vomiting (P=0.921), and diarrhea (P=1.0). Five patients in the ILRT boost arm and three in the EBRT alone arm experienced stricture, while no cases of fistula formation were reported. Conclusion: Dose escalation with ILRT can result in an enhanced CR accompanied by manageable toxicity, ultimately leading to improved locoregional control.

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.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy

Introduction: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. Methods: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. Results: Twenty-seven patients (51%) were treatment naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival for ETS ≥20% and Conclusion: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

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.

Efficacy of Nimotuzumab plus Concurrent Chemo-Radiotherapy for Unresectable Esophageal Cancer: A Real-World Study

The esophageal cancer ranked 7th in the morbidity of malignant cancer and the 6th contributed to carcinoma deaths. Most patients are diagnosed of advanced stage at first visiting. The 5-year survival rate of unresectable esophageal cancer is about 20% after the standard treatment of concurrent chemo-radiotherapy. Nimotuzumab, a humanized anti-EGFR antibody, has shown good efficacy and low toxicity in epithelial tumors. This two-center, real-world study evaluated the efficacy and safety of nimotuzumab combined with concurrent chemoradiotherapy in unresectable esophageal squamous cell carcinoma (ESCC). Totally 503 eligible unresectable ESCC patients from Jan 2014 to Dec 2020 were included. 1:2 nearest neighbor propensity score matching (PSM) was performed to match the Nimo group (nimotuzumab plus concurrent chemo-radiotherapy) and CRT group (concurrent chemo-radiotherapy), and the covariates included age, gender, tumor location, lesion length, TNM stage, clinical stage, and radiotherapy dose. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 61 patients were in Nimo group which received nimotuzumab (200 mg/w, 4-6 weeks) combined with concurrent chemo-radiotherapy (chemotherapy: S-1/FP/TP/DP for 2-4 cycles; radiotherapy: 2DRT,3D-CRT or IMRT, 50-70 Gy in 25-35 fractions) and 107 patients in CRT group only received concurrent chemo-radiotherapy. The baseline characteristics were well balanced between the two groups. The efficacy of Nimo group was better than that of CRT group. The ORR was 85.2% vs. 71.0%, (P=0.037), the DCR was 98.4% vs. 91.6%, (P>0.05). The median PFS was 28.07 months vs. 19.54 months, and the 1-, 3- and 5-year PFS rates were 78.2% vs. 72.9%, 37.5% vs. 28.3%, and 29.1% vs. 21.3%, respectively (HR: 0.6860, 95% CI: 0.4902-0.9600, P=0.034). The median OS was 34.93 months vs. 24.30 months and the 1-, 3- and 5-year OS rates were 88.5% vs. 81.3%, 46.8% vs. 35.2% and 37.4% vs. 28.0%, respectively (HR: 0.6701, 95% CI: 0.4792-0.9372, P=0.024). The adverse events including radiation esophagitis, radiation pneumonitis, bone marrow suppression, nausea, vomiting, and rash were no significantly different between the two groups (P>0.05). Nimotuzumab combined with concurrent chemo-radiotherapy improved the ORR, and prolonged PFS and OS in unresectable ESCC patients with a good tolerance.

Efficacy and Safety of First-line Therapies for Advanced Unresectable Oesophageal Squamous Cell Cancer: a Systematic Review and Network Meta-analysis

AimTo compare the clinical efficacy and safety of first-line treatments for advanced unresectable oesophageal squamous cell cancer. Materials and methodsA systematic review and network meta-analysis was carried out by retrieving and retaining relevant literature from databases. The studies were randomised controlled trials comparing first-line treatments for advanced unresectable oesophageal squamous cell cancer. A Bayesian network meta-analysis was used to assess clinical outcomes. ResultsNine studies including 4499 patients receiving first-line treatments were analysed. For all populations, toripalimab plus chemotherapy tended to provide the best overall survival (hazard ratio 0.58, 95% confidence intervals 0.43–0.78) and sintilimab plus chemotherapy provided the best progression-free survival (0.56, 0.46–0.68). Nivolumab plus chemotherapy presented the best objective response rate (odds ratio 2.45, 1.78–3.42) and camrelizumab plus chemotherapy (0.47, 0.29–0.74) appeared to be the safest. Sintilimab plus chemotherapy (0.55, 0.40–0.75) and nivolumab (0.54, 0.37–0.80) plus chemotherapy had the best overall survival in programmed death ligand 1 (PD-L1) tumour proportion score <1% and ≥1% subgroups. Toripalimab plus chemotherapy (0.61, 0.40–0.93) and pembrolizumab (0.57, 0.43–0.75) were the best in overall survival in combined positive score <10 and ≥10 subgroups, respectively. Toripalimab plus chemotherapy showed the best overall survival in the Asian group; pembrolizumab presented better overall survival in the Asian population than the non-Asian group. ConclusionMost immunotherapy combined with chemotherapy showed superior clinical benefits and sintilimab plus chemotherapy, toripalimab plus chemotherapy and tislelizumab plus chemotherapy had better comprehensive clinical efficacy. PD-L1 expression detection and ethnicity differences are still of great significance and most suitable regimens varied from each subgroup.

Predictive values of the hemoglobin, albumin, lymphocyte and platelet score (HALP) and the modified -Gustave Roussy immune score for esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy

The hemoglobin, albumin, lymphocyte and platelet (HALP) score and the Gustave Roussy immune score (GRIm⁃Score) are prognostic markers in several types of malignant tumors. The prognostic values of HALP score and GRIm⁃Score in concurrent chemoradiotherapy for unresectable esophageal cancer remain unknown. MethodsWe enrolled 150 esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy in our institution between 2013 and 2018. The cutoff values for HALP, and GRIm⁃Score were defined by using receiver’s operating characteristic curves. Survival was analyzed with the Kaplan– Meier method, with differences analyzed with the log-rank test. Multivariate Cox proportional-hazards models were used to evaluate the prognostic significance of HALP and GRIm for ESCC. ResultsHALP was significantly associated with the Zubrod ECOG WHO performance status, tumor location, and the clinical tumor, node, metastasis stage. Modified GRIm (mGRIm) was only significantly associated with metastasis / recurrence before radiotherapy (χ2 = 6.25). Univariate Cox regression analysis showed that higher mGRIm (HR 1.9 95%CI 1.3–2.9) and lower HALP (HR 2.4 95%CI 1.6–3.7) were all associated with worse OS. Multivariate COX analysis found that higher mGRIm score (HR 1.7 95%CI 1.1–2.6), and lower HALP score (HR 2 95%CI 1.3–3.2) were both independent risk factors of overall survival. The nomogram c-index in inside validation was 0.66. ConclusionBoth HALP and mGRIm are independent prognostic factors for patients with unresectable ESCC.

Comparison of Short-term Outcomes Between Esophageal Bypass Surgery and Self-expanding Stent Insertion in Esophageal Cancer: A Propensity Score-matched Analysis Using a Large-scale Inpatient Database.

Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7d, P = 0.003). Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.

Low muscle mass measured at T12 is a prognostic biomarker in unresectable oesophageal cancers receiving chemoradiotherapy

Background and purposeLow muscle mass is an imaging biomarker of patient frailty that has been associated with increased toxicity and decreased survival in a number of cancers. Patients with unresectable oesophageal cancer receive chemoradiotherapy as standard of care. Muscle mass is not yet an established prognostic marker in this population.Muscle mass is usually assessed by segmenting skeletal muscle at the L3 vertebral level. But radiotherapy planning scans for oesophageal cancers do not always image this level, which has limited previous studies of body composition. Skeletal muscle is known to regulate immune function, but the association of muscle mass with lymphopenia in cancer patients has not been shown. Materials and methodsWe retrospectively analyse 135 oesophageal cancer patients who received chemoradiotherapy and investigate the prognostic value of skeletal muscle area assessed at T12. We also examine the association between muscle mass and radiation-induced lymphopenia. ResultsWe find that low muscle mass is associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.72 [0.53–0.97]). However, this effect interacts with body mass index (BMI) such that the prognostic value of low muscle mass is removed by high BMI. In our study, patients with low muscle mass were more prone to radiation-induced lymphopenia (75% vs. 50% in patients with high muscle mass). A significant decrease in circulating lymphocytes was associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.68 [0.47–0.99]). ConclusionOur study shows that assessing muscle mass at T12 is feasible and provides prognostic information. Low muscle mass at T12 is associated with poorer overall survival and increased risk of radiation-induced lymphopenia. Muscle mass provides additional information over performance status and BMI. Low BMI patients are most affected by low muscle mass, highlighting the importance of close nutritional support in this population.

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.

Phase II trial of terelizumab combined with radiotherapy of locally advanced unresectable esophageal squamous cell carcinoma: TREC trial.

e16086 Background: Concurrent chemoradiotherapy (CCRT) is the standard therapy for locally advanced unresectable esophageal squamous cell cancer (ESCC)，However, some patients cannot tolerate or are unwilling to CCRT. The aim of this phase II trial was to assess the efficacy and safety of the tirelizumab combined with radiotherapy in patients of locally advanced unresectable ESCC. Methods: Key eligibility criteria were as follows: ESCC of clinical stage Ⅱ-Ⅳa; aged 18 to 90 years; cannot tolerate or are unwilling to CCRT; ECOG performance status 0 or 1; and performed radiotherapy: Involvement field irradiation, nodal GTV (GTVn) (regional lymphatic metastasis) radiotherapy dose 60Gy, the esophageal gross tumor volume (GTVt) radiotherapy dose 50Gy, if the gastroscope pathology is completely relieved, otherwise it is 60Gy. All patients registered before radiotherapy. The patient received concurrent therapy with tirelizumab (200mg every time, 3-week cycle), until the disease progresses or clinical benefits are lost (the longest time is 12 months). The primary endpoint was the esophageal gross tumor pathological complete remission rate (pCR). Results: Between 01 August 2021 and 31 December 2022, 31 patients were enrolled, and 27 completed radiotherapy and at least two times of tirelizumab treatment. Data cutoff date was 31 January 2023, median follow-up time among survivors after radiotherapy was 9 months (range 4-20). The esophageal gross tumor pCR rate was 66.7% (95% CI, 14.3%-52.3%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 48.1%; grade 3, 7.4%; grade 4-5, no). No treatment-related mortality occurred. Two (7.4%) patients had tumor recurrence and two (7.4%) patients died (Infection and heart disease). The 1-year PFS rate, median PFS and median OS had not been reached yet. For locally advanced unresectable ESCC that can't receive CCRT, the combination of tirelizumab and radiotherapy shows promising efficacy and acceptable toxicity, providing a feasible and effective choice. The research of long-term survival analysis is under way. Conclusions: Concurrent radiotherapy with tirelizumab shows promising efficacy and controllable safety for patients with locally advanced ESCC who are unable or unwilling to undergo CCRT, and warrants further evaluation in larger studies. Clinical trial information: ChiCTR2100053182 .

PD-0890 Efficacy of nimotuzumab plus concurrent chemoradiotherapy for unresectable esophageal cancer

PD-0890 Efficacy of nimotuzumab plus concurrent chemoradiotherapy for unresectable esophageal cancer

Efficacy of Aidi injection combined with chemotherapy, radiotherapy or chemoradiotherapy for unresectable esophageal cancer treatment: A meta-analysis and systematic review of 29 randomized controlled trials based on Asian populations (China).

This study aimed to assess the efficacy of Aidi combined with standard treatment, including radiotherapy (R), chemotherapy (C), or chemoradiotherapy (CR), for unresectable esophageal cancer (EC). Eight online databases were queried to collect randomized controlled trials (RCTs) published from database construction to August 2022. Patients in the control group underwent standard treatment with R, C, or CR, whereas those in the experimental group underwent Aidi combined with standard treatment. In this meta-analysis, 29 reports with 2079 patients were included. The results showed that the Aidi-based combination therapy groups had higher objective response rates (ORRs), disease control rates (DCRs), one-year overall survival (OS) and improvement and stability of Karnofsky performance status (KPS) than the control group (risk ratio (RR) = 1.24 (95% CI = 1.17-1.33), 1.09 (95% CI = 1.05-1.14), 1.50 (95% CI = 1.31-1.72), and 1.28 (95% CI = 1.16-1.41)). The Aidi-based combination therapy groups also had lower total incidence rates of bone marrow suppression (BMS), chemotherapy-induced nausea and vomiting (CINV) and radiation esophagitis (RE) than the control group (RR = 0.48 (95% CI = 0.41-0.56), 0.46 (95% CI = 0.36-0.58), and 0.49 (95% CI = 0.38-0.62)). In addition, subgroup analysis suggested that the optimal dose and cycle of Aidi injection combined therapy was 80-100ml/time and 30days/2 cycles. The efficacy of Aidi combined with DP (docetaxel + cisplatin) was better than the Aidi combined with PF (cisplatin plus fluorouracil). Aidi-based combination therapy showed high efficacy for unresectable EC treatment and reduced the incidence rates of adverse events. However, further studies including higher-quality RCTs are needed to validate these findings. INPLASY 202290020.

Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.

Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer. The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis. After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust. PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.

Laparogastroscopy-A Transgastric Laparoscopic Approach for Malignant Esophageal Stenosis.

This paper presents the laparogastroscopy procedure, a mini-invasive, palliative method as an alternative to gastrostomy to be recommended by gastroenterologists. Laparogastroscopic stenting with endoluminal transtumoral drilling solves the problem of oral nutrition in patients with unresectable esophageal cancer, avoiding percutaneous feeding. The results of this technique are presented in a retrospective analysis of a study group of 63 patients with advanced esophageal carcinoma admitted between January 2015 and December 2020 at Department of General Surgery of Emergency County Hospital Sibiu, Romania, in terms of post-operative morbidity and mortality. The type of stents used were Pezzer prostheses (48.6%), silicone prostheses (31.9%), and self-expanding metal stents (6.9%). Eight patients (12.7%) had fistulas (at admission to the clinic), which were successfully sealed. Post-operative dysphagia was absent in most patients and minimal in 16.6% of patients, so all patients could initiate oral feeding, improving their nutritional status. The average length of hospitalization for all patients was 9.22 ± 5.05 days. The most frequent local complications were restenosis (9.5%), stent displacement (7.9%), and bleeding (4.8%). The mean survival time was 10.75 ± 15.72 months. Laparogastroscopic stenting could be a valuable alternative in palliative esophageal cancer surgery, improving the quality of life and nutritional status in patients unsuitable for endoscopic stenting.

Definitive chemoradiotherapy in elderly patients with esophageal cancer: Safety and outcome

AbstractObjective: The efficacy and safety of definitive chemoradiotherapy (dCRT) for elderly patients with unresectable esophageal cancer (EC) are not yet fully understood. We conducted this study to evaluate the outcome and toxicity in elder patients (65 years and over) of unresectable EC treated with dCRT.Methods: From four Georgian cancer centers with a radiation oncology department, we identified 44 elderly patients with EC suitable according to the study criteria. Overall survival (OS) was estimated from the beginning of treatment and toxicity scored using CTCAE 5.0 criteria.Results: The median age of patients was 70.0 years (range 65–83 years), with male predominance (77.3%) and 59% of patients were with Eastern Cooperative Oncology Group (ECOG) performance status 1. Because of significant dysphagia (grade 3–4) nine patients underwent intervention (stenting or gastrostomy) before dCRT. More than two‐thirds of patients were squamous cell histological type (77.3%). Localization of tumors was equally distributed between the middle and lower parts of the esophagus (38.6%) and in 26 patients (59.1%) tumor length was more than 5 cm. The majority of patients had stage III disease (61.4%).Median survival was 16.0 months (95% confidence interval [CI] 0–35.9). OS at 12 and 24 months was 53.7% and 43.6%, respectively. Fifteen patients (34%) were alive from 2.1 to 5.4 years after treatment. A statistically significant difference (p = 0.011) in median OS was found between patients who received full (not reached) versus overall survival (OS) was 9.0 months in patients who received nonfull dose of radiotherapy (RT) (95% CI 2.79–15.2). Additional analysis between age subgroups revealed that elder subgroup patients (&gt;75 years) had the highest OS, compared to younger (65–70 years) and intermediate groups (71–75 years) (p = 0.001). The most common adverse events were grade 3–4 leukopenia (43.2%), anemia (29.5%), and esophagitis (27.3%).Conclusion: The results of our study support the feasibility and efficacy of dCRT for unresectable EC in carefully selected elderly patients. Survival was correlated to complete dose of RT and therefore accurate selection of patients is crucial for better long‐term survival. Our study showed that chronological age alone does not reflect a patient's ability to tolerate dCRT. Toxicity of dCRT is always a very important issue and patient selection must be very cautious in geriatric patients, although dCRT might benefit highly selected patients.

Safety and efficacy of conversion therapy for esophageal squamous cell carcinoma.

362 Background: The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable esophageal squamous cell carcinoma (ESCC) after initial treatment. Conversion therapy has been commonly defined as treatment aiming at a curable intention after tumors initially deemed technically or oncologically unresectable or only marginally resectable respond to chemotherapy. In our institute, conversion therapy is considered for patients with para-aortic lymph node-positive advanced ESCC who have no other distant metastasis, if the para-aortic lymph node metastases have disappeared after systemic chemotherapy. Methods: There were 33 patients of unresectable esophageal cancer with positive para-aortic lymph node metastases from 2011 to 2021. Nine of these patients showed disappearance of para-aortic lymph node metastases and underwent conversion therapy, seven patients underwent esophagectomy and two patients underwent chemoradiation therapy (CRT). Characteristics, short-term and long-term results of these nine cases are studied. Results: All of the nine patients who had para-aortic lymph node metastases were treated with induction DCF (Docetaxel + Cisplatin + 5-FU) therapy as initial treatment. After disappearance of para-aortic lymph node metastasis, minimally invasive or open esophagectomy was performed in seven patients and CRT was performed in two patients. In operation group, four patients (57%) had Clavien-Dindo grade 2 or 3 complications, but no perioperative death was observed. In CRT group, there was no toxicity over CTCAE grade 3. Four of nine patients (44%) had recurrence, within mediastinum lymph node, abdominal lymph node or adrenal gland. 3-year DFS was 56% and 3-year OS was 67%. Conclusions: Conversion therapy is safe and feasible in cases that responded to systemic chemotherapy. Some cases showed good prognosis. Long-term survival is expected with conversion therapy. In our study, there was few cases that could led to conversion therapy. It is expected that more aggressive initial chemotherapy will be used in the future for patients with positive para-aortic lymph node metastases with a view to conversion therapy.

Docetaxel, Cisplatin, and 5-FU Triplet Therapy as Conversion Therapy for Locoregionally Advanced Unresectable Esophageal Squamous Cell Carcinoma.

The standard treatment for locoregionally advanced unresectable esophageal squamous cell carcinoma was radical chemoradiotherapy. However, the prognosis was modest. Emerging evidence showed the concept of induction chemotherapy with a goal of conversion surgery. We reviewed the long-term, clinical outcomes and safety data of induction chemotherapy using docetaxel-cisplatin-5FU (DCF) and subsequent definitive treatment, either surgery or radical chemoradiotherapy (CRT), in locally advanced unresectable esophageal cancer in Queen Mary Hospital, Hong Kong. A total of 47 patients (median age 62 years, male: 41 (87.2%)) with locoregionally advanced unresectable esophageal cancer received induction DCF. The response rate was 65.9% (complete/partial response: n = 31). After induction DCF, 24 patients (41.4%) had radical surgery and 7 (14.9%) had definitive CRT. The median overall survival (mOS) was significantly longer in patients received subsequent surgery compared with those with definitive CRT (mOS: 40.2 vs. 9.1 months, hazard ratio 3.33, 95% confidence interval 1.22-9.07, p = 0.02) and no definitive treatment (mOS: 40.2 vs. 6.3 months, hazard ratio 8.51, 95% confidence interval 3.7-19.73, p < 0.001). Patients who received surgery, female, and those with supraclavicular lymph node involvement had a better OS. Twenty-one patients (44.7%) developed grade 3/4 adverse events during induction DCF, and two died after chemotherapy because of trachea-esophageal fistula complicated with sepsis. Eleven patients who had surgery had postoperative complications and none had postoperative mortality. Induction DCF and subsequent conversion surgery offered a chance of cure with long-term survival benefit and manageable toxicities in patients with locoregionally advanced unresectable esophageal cancer.

Risk Factors of Treatment-Related Pneumonitis after Thoracic Radiotherapy/Chemoradiotherapy Combined with Anti-PD-1 mAb in Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Treatment-related pneumonitis (TRP) and radiation recall pneumonitis (RRP) has recently been identified as a toxicity triggered by thoracic irradiation combined with anti-PD-1 mAb in esophageal squamous cell carcinoma (ESCC). However, the incidence, risk factors and dose-volume parameters remain unknown. <h3>Materials/Methods</h3> We analyzed 97 patients with ESCC who received thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 mAb. There were 74 patients of newly diagnosed/locally advanced unresectable esophageal cancer, 22 patients of recurrent after radical resection /metastatic esophagus cancer, and 1 patient of resectable esophageal cancer with neoadjuvant therapy. 41 patients received concurrent thoracic radiotherapy and anti-PD-1 mAb, 56 patients received sequential thoracic radiotherapy and anti-PD-1 mAb. The median radiation dose of PTV was 59.4Gy (range from 45Gy to 66Gy, 1.8Gy-2.2Gy per fraction). TRP and RRP were classified according to the CTCAE version 5.0 and the effect of dose-volume parameters of lung on TRP and RRP was analyzed. <h3>Results</h3> The average value of V_5, V_10, V_20, V₃₀ and MLD of lung was 49.2% (27.9%-73.6%), 35.9% (21.7%-48.6%), 21.3% (12.7%-29.9%), (1.5% -17.5%) and 1092.5cGy (666.9cGy-1569.6cGy), respectively. The incidence of TRP was 46.4% (45/97). 41.2% of patients developed grade 1 or 2 pneumonitis and 4.1% of patients was grade 3 pneumonitis. Of note, there was 1 death probably related with TRP. The incidence of RRP was 14.4% (14/97). 14.4% of patients developed grade 1 or 2 pneumonitis and there was no grade ≥3 RRP. The median onset time of TRP and RRP was 16 weeks after receiving anti-PD-1 mAb (2.6 weeks-65.9 weeks) and 48.9 weeks (27 weeks-91.1 weeks) after thoracic radiotherapy, respectively. Result of multivariate analysis showed that V₅ was an independent risk factor of grade ≥2 TRP (P=0.003, OR=1.106). The incidence of grade ≥2 TRP in the V₅≥55.7% group was significantly higher than that in the V₅<55.7% group (56.5% vs 16.2%). There was only a trend towards higher V₅, V₃₀, V₃₅, and MLD related to RRP without statistical significance. <h3>Conclusion</h3> We demonstrate a high risk of TRP in ESCC patients receiving thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 mAb and mostly pneumonitis was grade 1 and grade 2. While the occurrence of RRP is relatively less and the severity is mild. TRP (grade≥2) is associated with V₅≥55.7%, so clinicians should pay more attention to restriction of V₅ and V₅<55.7% might be a safer volume. Therapy strategy combined thoracic radiotherapy/chemoradiotherapy with anti-PD-1 mAb might be a safe choice, it is worth a further exploration.