Metastatic Esophageal Carcinoma Research Articles

A novel case of simultaneous tracheal stenting and endobronchial valve (EBV) deployment for tracheal stenosis and persistent air leak guided by an endobronchial collateral ventilation assessment system and digital chest drain in malignant esophageal carcinoma.

Persistent air leak may complicate malignant disease of the thorax, causing significant morbidity and mortality. A 51-year-old male with a 30-pack-year history of smoking was diagnosed with metastatic esophageal carcinoma with invasion into the right upper lobe of the lung. He developed a large right hydropneumothorax complicated by empyema leading to persistent air leak despite the insertion of two chest drains. Computed Tomography imaging with 3-dimensional reconstruction showed severe tracheal compression from the enlarging esophageal tumour as well as bronchopleural fistulas in the right upper lobe. Rigid bronchoscopy with metallic tracheal stenting was performed. This was followed by localization and quantification of air leak with an endobronchial collateral ventilation assessment system and a digital chest drain to guide endobronchial valve placement, in a single operative procedure. This novel combination of interventional bronchoscopy techniques enabled successful transition to an ambulatory chest drain and subsequent hospital discharge.

Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

A phase 1/2, open-label, multicenter, dose escalation and cohort expansion study of the safety and efficacy of anti-CD70 allogeneic CRISPR-Cas9–engineered T cells (CTX131) in adult patients with relapsed or refractory solid tumors.

TPS2676 Background: CD70, a type II transmembrane protein and member of the tumor necrosis factor (TNF) receptor family, demonstrates high expression across multiple malignancies making it an attractive target for chimeric antigen receptor (CAR) T cell therapy. CD70 is expressed in 80% of clear cell renal cell carcinoma (ccRCC) and in 40-60% of cervical carcinoma (CC), esophageal carcinoma (EC), pancreatic adenocarcinoma (PAC), and pleural mesothelioma (PM) (1). CTX131 is a CD70-directed allogeneic CAR T cell investigational product manufactured ex vivo from healthy donor T cells using CRISPR/Cas9 technology. Genetic modifications in CTX131 include targeted insertion of a CD70-directed CAR construct, and targeted disruption of 5 loci: TRAC (to reduce risk of GvHD), B2M (to improve persistence in the allogeneic setting), CD70 (to reduce fratricide and improve anti-tumor function), TGFBR2 (to reduce immunosuppressive effect of TGFB in the tumor microenvironment), and Regnase-1 (to improve functional persistence) (2). Preclinical studies show the combination of TGFBR2 and Regnase-1 disruption in CTX131 works synergistically to enhance anti-tumor activity, inhibit tumor growth in xenograft mouse models, prolong survival, and increase central memory T cell populations (3). Methods: We are conducting a phase 1/2 study in patients (pts) with unresectable or metastatic ccRCC, CC, EC, PAC, and PM. Part 1 is a dose escalation with two separate cohorts, one for ccRCC pts and another for CC, EC, PAC, and PM pts. Part 1 ccRCC cohort began recruiting in 2023. Part 2 is a single-arm expansion of disease-specific cohorts. Key eligibility criteria include at least one prior line of standard treatment, ECOG status 0-1, evaluable disease per RECIST v1.1 (or modified RECIST1.1 for PM), adequate hematologic and organ function, and availability of tumor tissue for CD70 IHC. Key exclusion criteria include prior treatment with CD70-targeting agents and active CNS metastasis. Pts will receive standard lymphodepleting chemotherapy with fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 daily x 3 days followed by CTX131 IV infusion at doses ranging from 30-900 million cells in 4 dose level cohorts. Redosing with CTX131 is permitted. For Part 1, the primary endpoint is DLTs with secondary endpoints including ORR, DOR, PFS, and OS. For Phase 2 the primary endpoint is ORR by IRC assessment. The trial is currently open with enrollment ongoing. 1. Flieswasser et. al. 2019. 2. Mai et. al. 2023. 3. Terrett 2023. Clinical trial information: NCT05795595 .

Capecitabine and oxaliplatin induced Steven-Johnson syndrome following nivolumab in a patient of metastatic esophageal carcinoma.

Stevens-Johnson syndrome presents as mucocutaneous blistering and sloughing, which may follow a devastating clinical course. Although Stevens-Johnson syndrome has been reported following the administration of anticancer drugs, only a few cases induced by cytotoxic anticancer drugs, administered after immune checkpoint inhibitors, have been reported. The present report describes a case of Stevens-Johnson syndrome caused by capecitabine and oxaliplatin (CAPEOX) combination chemotherapy, in a patient with esophageal squamous cell carcinoma, who had been previously treated with nivolumab.

Exceptional Response to Olaparib: A Case Report of Metastatic Esophageal Squamous Cell Carcinoma in a Patient With Fanconi Anemia, Germline FANCA Mutation, and Somatic BRCA2 Mutations.

Exceptional response to olaparib in a case with Fanconi anemia and metastatic esophageal carcinoma

Abscopal effect of radiation in metastatic esophageal carcinoma: fourth reported case.

Abscopal or bystander effect of radiotherapy is a rare and unpredictable outcome encountered during treatment of metastatic cancer where tumor regression is observed distant from irradiated volume. While it has been more frequently reported with malignancies like melanoma, lymphoma, and renal cell carcinoma, data regarding metastatic esophageal cancers are sparse. We describe a case of abscopal regression of distant mediastinal and upper abdominal lymph nodes in a 65-year-old gentleman whose primary esophageal tumor was irradiated with hypo-fractionated radiotherapy in an attempt to achieve local palliation. Our case study emphasizes the systemic benefit of local radiotherapy and the need for future research to investigate its utility as this clinical event poses widespread response in an otherwise dismal Stage-IV cancer with minimal treatment-related side effects.

CLO23-064: PD-1/PD-L1 Inhibitors in Advanced and Metastatic Esophageal Carcinoma: An Updated Meta-Analysis of Randomized Controlled Trials

"CLO23-064: PD-1/PD-L1 Inhibitors in Advanced and Metastatic Esophageal Carcinoma: An Updated Meta-Analysis of Randomized Controlled Trials" published on 31 Mar 2023 by National Comprehensive Cancer Network.

The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma.

The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.

Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review

Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review

RWD123 Real-World Data About Treatment Pattern and Outcomes of Patients With Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma in France: Results From the Fregat Database

Esophageal cancer is the seventh most common cancer and sixth leading cause of cancer death, worldwide, with approximately 600,000 new cases and over 540,000 deaths in 2020. Squamous-cell carcinoma accounts for approximately 60% of cases in Europe. The study aim was to describe real-world treatment and outcomes of French patients presenting with UnResectable Advanced, or Metastatic Esophageal Squamous-Cell Carcinoma (URAM-ESCC) from 2014 to 2019 before approval of immune-checkpoint inhibitors (ICI).

A Case Report Successful Treatment the Patient with Squamous Esophagus Cancer IV Stage

In this study, we described a clinical case of unoperable squamous carcinoma in the thoracic esophagus, demonstrating the effectiveness of induction chemotherapy followed by independent chemoradiotherapy and brachytherapy in patients with metastatic esophageal carcinoma. The patient was treated with induction chemotherapy, concurrent chemoradiation with weekly carboplatin AUC 2 and paclitaxel 50 mg/m2 and brachytherapy. The most characteristic feature of this clinical case is that the use of brachytherapy in the complex treatment of patients with esophageal carcinoma allows increasing the dose in the target without increasing the risk of complications associated with the escalation of the radiation dose. Brachytherapy can achieve very high rates of local control with a reduction in morbidity, compared with external beam radiation therapy. In most patients, esophageal carcinoma is diagnosed at stages III–IV of the disease. Squamous cell esophageal carcinoma is an aggressive disease that, depending on the prevalence, requires various treatment methods, the search for the optimal one is still ongoing. The main standard of treatment in inoperable patients with squamous cell esophageal carcinoma is self — chemoradiotherapy. However, in patients with unoperable esophageal carcinoma, it is also possible to use induction chemotherapy followed by independent chemoradiotherapy and brachytherapy. The combined use of these methods of treatment in conditions of impossibility of surgical intervention is the method of choice in patients with stage III–IV of the disease. The standard dose of DLT for squamous carcinoma of the esophagus is 50.4 Gy. In the conducted studies, it was shown that the escalation of the dose to the tumor using remote radiation therapy leads to an increase in severe post-radiation injuries and an increase in the frequency of deaths. Induction chemotherapy plus concurrent chemoradiotherapy and brachytherapy to boost tumor, and improves disease control and survival.

1241P Phase Ib study of futibatinib plus pembrolizumab in patients with advanced or metastatic solid tumors: Tolerability results and antitumor activity in esophageal carcinoma

Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for cancer patients (pts). Here, we report the safety and tolerability of FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic solid tumors and first results for preliminary antitumor activity in pts with esophageal carcinoma (EC). This study consists of Feasibility phase (FP) and Expansion phase (EP). In FP, pts with adv or metastatic solid tumors harboring FGF/FGFR abnormalities received futibatinib 20 mg once daily (QD) plus pembrolizumab 200 mg every 3weeks. In EP, pts with ICIs naive (Cohort A) or ICIs refractory (Cohort B) for adv or metastatic EC harboring FGFR mRNA overexpression who have received at least one prior therapy with a fluorouracil and platinum-based drug received futibatinib plus pembrolizumab at the recommended dose (RD) determined in FP. Primary endpoint was dose-limiting toxicity (DLT) in FP and overall response rate (ORR) in EP; Secondary endpoints included treatment-related adverse events (TRAEs) and disease control rate (DCR). As of November 29, 2021, 11 pts in FP, 9 pts (Cohort A) and 10 pts (Cohort B) in EP were enrolled. No DLTs were observed in FP and the RD of futibatinib in combination with pembrolizumab was determined 20 mg QD. Most common TRAEs in FP (N=11; all grade, grade ≥3) were hyperphosphatemia (91%, 27%), nausea (36%, 0%) and diarrhea (27%, 0%). As results of the interim analysis in EP, confirmed partial responses (PRs) were observed in 4 pts with squamous cell carcinoma (sq) in Cohort A; ORR was 44% with DCR of 78%. In Cohort B, confirmed PRs were observed in 2 pts [1 sq pt; 1 adenocarcinoma (adeno) pt]; ORR was 20% with DCR of 60%. Futibatinib plus pembrolizumab showed well-tolerability and manageable safety profile in pts with adv or metastatic solid tumors. Preliminary antitumor activity was observed not only in ICIs naïve but also in ICIs refractory adv or metastatic EC pts regardless of sq and adeno. Enrollment in EP is ongoing including an additional cohort for ICIs naïve 1st line adv EC and ICIs refractory adv NSCLC pts.

Abstract 2421: Elucidation of CSF1 autocrine signaling mediated by mutant p53 in metastatic esophageal carcinoma

Abstract Introduction: Esophageal cancer is a highly aggressive cancer and is the 6th leading cause of cancer mortality worldwide, with esophageal squamous cell carcinoma (ESCC) being the most prevalent subtype. Mutations in the tumor suppressor TP53 (human homolog of mouse Trp53), which encodes p53, are detected frequently in ESCC that in turn correlate with poor survival and high metastatic rates. We have conducted RNA-Seq and cytokine array on primary and metastatic tumor cells harvested from our mouse models with Trp53R172H mutation. We have identified colony stimulating factor 1 (CSF1) to be upregulated. Our data suggest the existence of CSF1-CSF1R autocrine signaling, and its functional relationship to the promotion of metastasis in ESCC, recognizing that CSF1 is known to be critical in the polarization of macrophages to M2-like tumor associated macrophages. Our goal is to investigate the role and mediators of CSF1/CSF1R signaling by which missense TP53 mutations can promote invasion and lung metastasis in ESCC. Methods: We used L2-Cre; LSL-Trp53R172H; Rosa26LSL-YFP mice and 2D/3D cell culture systems to model ESCC. To assess the functional role of CSF1, we established a CRISPR approach to knockout Csf1in our cells introducing ribonucleoprotein (RNP) Cas9/gRNA complex via nucleofection and overexpressed Csf1. We also utilized a small molecule inhibitor of CSF1R, GW2580. We conducted TCGA analysis on the association of distinct TP53 mutations with ESCC prognosis and Csf1 expression, as well as Csf1 expression in metastatic tumors. Based on this, we modeled ESCC by introducing various DNA contact and conformational p53 mutations into esophageal cells with wildtype p53 via base editing. Results: TCGA data and our models demonstrate that metastatic ESCCs have increased Csf1 expression compared to primary tumors and it is dependent upon p53 mutation status. In addition, analysis of ESCC patients’ datasets reveal that specific p53 mutations are associated with markedly differential overall survival rates and Csf1 expression. We show that Csf1 function is related to tumor cell invasion, primary tumor growth and metastatic tumor burden in a mutant p53 background. We have identified both bromodomain and extra-terminal motif (BET) protein BRD4 and transcription factor nuclear factor kappa B (NF-κB) as proteins that interact with Trp53R172H at higher levels compared to wildtype p53 to induce Csf1 expression. In addition, inhibition of CSF1R with small molecule GW2580 downregulated JAK-STAT3 pathway mediating epithelial-mesenchymal transition (EMT) mechanisms that would contribute to increased invasiveness and metastasis. Conclusion: We have demonstrated novel roles and mechanisms of mutant p53-dependent CSF1-CSF1R autocrine signaling and its mediators in promoting lung metastasis from ESCC that may be applicable to other squamous cell cancers. We believe this mechanism can be targeted therapeutically. Citation Format: Gizem Efe, Qiaosi Tang, Ricardo Cruz-Acuna, Kensuke Suzuki, Kensuke Sugiura, Joel Gabre, Uma Sachdeva, Wei Gu, Carol L. Prives, Anil K. Rustgi. Elucidation of CSF1 autocrine signaling mediated by mutant p53 in metastatic esophageal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2421.

REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors—Results of the oesophageal or gastric carcinoma (OGC) cohort.

4060 Background: Combination VEGF and PD-1/PD-L1 axis blockade has shown benefit in various tumors and is emerging as a promising combination strategy. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of regorafenib (R) (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in advanced or metastatic oesophageal or gastric carcinoma (OGC) patients (pts). The primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Dec. 2018 and Mar. 2021, 49 pts were enrolled in 6 centers: 33 adenocarcinoma (ADK), 16 squamous cell carcinoma (SCC). Median age was 63.9 (range 33 – 80). Median follow-up was 14.5 months. Median number of previous treatment lines was: 2 (range 1 – 6). 29 (59.2%) pts experienced at least 1 dose modification or treatment interruption due to an adverse event related to treatment. The most common grade 3/4 adverse events were : Hypertension (12.2% of pts), palmar-plantar erythrodysesthesia syndrome (10.2%), and hypophosphatemia (8.2%). No death was related to the treatment. Among the 42 (29 ADK and 13 SCC) pts who had at least one imaging tumor assessment, 8 (19.1%) achieved a partial response, 5 (17.2%) and 3 (23.1%) in the ADK and SCC group respectively. 12 pts (28.6%) demonstrated stable disease and 22 pts (52.3%) had progressive disease. The median PFS and OS were 1.9 months (95%CI 1.8 – 3.5) and 7.5 months (95%CI 4.5 – 15.7) respectively. Conclusions: The R+A combination is associated with encouraging antitumor activity in patients with OGC. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma

BackgroundFirst-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma.MethodsIn this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients).ResultsA total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P=0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P=0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P=0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P=0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone.ConclusionsBoth first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 648 ClinicalTrials.gov number, NCT03143153.)

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

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

Nivolumab in combination with radiotherapy for metastatic esophageal neuroendocrine carcinoma after esophagectomy: a case report

BackgroundMetastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time.Case presentationA man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography–computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography–computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.ConclusionsWe experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

A case report of esophageal metastasis from breast cancer

Abstract Introduction: The common metastatic sites of breast carcinoma are the lymph nodes, liver, lungs and bone. Breast cancer metastasis to esophagus is a rarity with an incidence of 0.03% to 0.6%. Patient concerns: A 63-year-old woman presented with worsening dysphagia of 13 months duration. Thirteen years before, the patient had a right modified radical mastectomy and radiotherapy treatment for breast carcinoma. Diagnosis: Barium swallow presented a stricture of 4 cm length in the midthoracic esophagus. On endoscopy, a stricture was found in the esophageal lumen at the 28th centimeter. Biopsy showed metastatic esophageal carcinoma. Interventions and outcomes: Chemotherapy with gemcitabine and capecitabine was provided as the treatment. After treatment, her dysphagia markedly improved. Conclusion: Esophageal involvement in metastatic breast cancer is rare. Dysphagia after breast cancer treatment can indicate metastasis. Histopathologic examination is required to confirm the diagnosis.

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.

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. ClinicalTrials.gov Identifier: NCT03691090.