Cervical Esophageal Carcinoma Research Articles

Combined Chemotherapy and Immunotherapy Induction for Screening of Patients with Cervical Esophageal Carcinoma for Subsequent Local Treatment: A New Treatment Paradigm.

Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.

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 .

Single-sEV profiling identifies the TACSTD2 + sEV subpopulation as a factor of tumor susceptibility in the elderly

BackgroundAging is a very complex physiological phenomenon, and sEVs are involved in the regulation of this mechanism. Serum samples from healthy individuals under 30 and over 60 years of age were collected to analyze differences in sEVs proteomics.ResultsBased on PBA analysis, we found that sEVs from the serum of elderly individuals highly express TACSTD2 and identified a subpopulation marked by TACSTD2. Using ELISA, we verified the upregulation of TACSTD2 in serum from elderly human and aged mouse. In addition, we discovered that TACSTD2 was significantly increased in samples from tumor patients and had better diagnostic value than CEA. Specifically, 9 of the 13 tumor groups exhibited elevated TACSTD2, particularly for cervical cancer, colon cancer, esophageal carcinoma, liver cancer and thyroid carcinoma. Moreover, we found that serum sEVs from the elderly (especially those with high TACSTD2 levels) promoted tumor cell (SW480, HuCCT1 and HeLa) proliferation and migration.ConclusionTACSTD2 was upregulated in the serum of elderly individuals and patients with tumors, and could serve as a dual biomarker for aging and tumors.

Larynx-Preserving Reconstructive Surgeries for Cervical Esophageal Carcinoma -Current Status and Future Prospects-

Larynx-Preserving Reconstructive Surgeries for Cervical Esophageal Carcinoma -Current Status and Future Prospects-

Patterns of Recurrence and Predictors of Outcome in Cervical Esophageal Carcinoma Patients Treated with Definitive Chemoradiation

Patterns of Recurrence and Predictors of Outcome in Cervical Esophageal Carcinoma Patients Treated with Definitive Chemoradiation

Larynx-preserving treatment strategy for patients with resectable cervical esophageal squamous cell carcinoma.

311 Background: Preservation of the larynx is an important treatment strategy for cervical esophageal squamous cell carcinoma (CESCC), because surgery for CESCC often involves laryngectomy. At our hospital, we actively perform dCRT (cisplatin + 5-fluorouarcil + radiation 60Gy) to preserve laryngeal function. In this study, we compared the treatment results of esophagectomy and definitive chemoradiation (dCRT) for resectable CESCC and examined larynx-preserving treatment strategies. Methods: Patients who were treated for resectable CESCC at our hospital from January 2003 to March 2019 were divided into surgery group and dCRT group for the initial treatment. All patients were eligible for both treatments. The treatment results were compared retrospectively. Results: Of all 61 patients, 23 patients received surgery and 38 received dCRT. There was no significant difference in patients’ characteristics between 2 groups. In surgery group, 19 cases lost their laryngeal function by surgery (82.6%). Recurrence was observed in 7 cases, of which only 3 case was local. In CRT group, 33 cases (86.8%) achieved complete response, of which 16 cases relapsed. 8 cases (21.1%) lost their laryngeal function by additional surgery after dCRT. There was no significant difference in 5-year survival rate between two groups (surgery, 60.8%; dCRT, 70.1%; p = 0.750). In dCRT group, 5-year laryngeal-preserving survival rate was 64.8%, and esophageal stenosis before treatment was the independent risk factor for non-larynx preservation. 5-year laryngeal-preserving survival rate was 78.5%, and 5-year survival rate was 85.4% for non-stenotic cases in dCRT group, which were significantly higher than those for stenotic cases. 5-year laryngeal-preserving survival rate was also high in the patients with Ce localized tumor (72.6%). In those patients, non-stenotic patients and cT1-T3 patients had significantly high 5-year laryngeal-preserving survival rate (87.5% and 92.3%). Conclusions: dCRT for CESCC was comparable to surgery in terms of long-term prognosis, and the rate of larynx preservation was high. Among the cases where the tumor was localized to Ce, the laryngeal preservation rate was particularly high in non-stenotic cases and cases with cT1-T3, and dCRT should be actively indicated for these cases.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

Do higher radiation doses improve survival for cervical esophageal squamous cell cancer patients treated with definitive chemoradiotherapy using intensity-modulated radiotherapy? A propensity-score matched analysis.

This study was conducted to determine whether higher doses of intensity-modulated radiotherapy (IMRT) could improve the survival rate in patients of cervical esophageal squamous cell carcinoma (CESCC), and lead to more severe treatment-related toxicity. The clinical records of stage I-IVA CESCC patients treated with definitive chemoradiotherapy (CRT) using IMRT between January 2013 and June 2018 were retrospectively analyzed. The patients in the high-dose (HD) group received ≥60 Gy and those in the standard-dose group received <60 Gy. A propensity score matching (PSM) was applied to balance the confounding factors between both groups. The primary endpoint was over-survival (OS). progression-free survival (PFS), loco-regional control (LRC), and treatment-related toxicity were also evaluated. A total of 136 patients with CESCC were included. Patients with N1-3 nodal and stages III-IVA of the disease (P < 0.05) were included in the HD group. The differences in the OS, PFS, and LRC between the two groups were not statistically significant (P = 0.350, 0.063, and 0.099, respectively). After PSM, significantly longer PFS and LRC were observed in the HD group. The difference in OS between the two groups was not statistically significant. There was no significant difference in the incidence of treatment-related toxicity between the two groups. The results of this PSM analysis suggested that higher doses may improve PFS and LRC for CESCC patients receiving CRT using OMRT, but do not demonstrate any statistically significant advantage in improving OS.

Elective Nodal Irradiation vs. Involved-Field Irradiation for Stage Ⅱ-Ⅳ Cervical Esophageal Squamous Cell Carcinoma Patients Undergoing Definitive Concurrent Chemoradiotherapy: A Retrospective Propensity Study with Eight-Year Survival Outcomes

Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the eight-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI). Patients with stage Ⅱ-Ⅳ CESCC treated with dCCRT in our institution between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission (AJCC) 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage (cT), clinical N stage (cN), clinical TNM stage (cTNM) and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated. The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 95.3 months (range, 28.0-186.2 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.5%, 39.0%, and 28.3%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.9%, 38.8% and 32.4% versus 45.2 months, 89.8%, 52.7%, 38.2%, 26.6%, respectively (P = 0.984; HR 0.99, 95% CI 0.61-1.62). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% versus 38.8%; P = 0.068 and 30.6% versus 14.3%; P = 0.089) at the end of dCCRT. Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

Treatment of cervical esophageal carcinoma: systematic review and meta-analysis

Objectives. Up to date managing a cervical esophageal carcinoma (CEC) has remained a controversial challenge. The choice of treatment is still uncertain. In the present review we attempted to assess eligibility of surgery in treatment of CEC. Material and Methods. We have enquired particular publication databases and the enquiries yielded 24 contributions matching study selection criteria such as (1) original articles published from 2000 to 2022, (2) primary tumor localization in the cervical esophagus, (3) squamous cell carcinoma, (4) available characteristics of studied groups (age, sex, T, N, M, stage), (5) detailed description of curative procedures (radiation therapy, chemotherapy, surgery), (6) information about overall survival. These publications represented two arms of 14 surgical and 17 non-surgical subgroups to analyze. Individual patient data and parameter estimates have been renewed on the basis of original Kaplan‒Meier curves plotted. Results. The analysis revealed a highly heterogeneous (I2 =83.76 %; 95 % CI, 71.40–92.16) random effects model. Including a surgical option into treatment of CEC did not affect 3-year overall survival (р=0.665); 46.4 % (95 % CI, 37.4–55.6) vs 43.7 % (95 % CI, 35.3–51.6), respectively. Possibilities of surgical and non-surgical modalities employment were discussed. Conclusion. In treatment of CEC CRT and surgery are non-inferior to each other. These modalities are evenly associated with posterior side effects and complications, which adversely affect functional outcomes and survival. The choice of a treatment mode may depend on tumor response to induction therapy. The latter demands further investigations.

Elective nodal irradiation versus involved-field irradiation for stage II–IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes

BackgroundDefinitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI).Materials and methodsPatients with stage II–IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated.ResultsThe 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8–182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61–1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT.ConclusionCervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

A prospective analysis of robotic three-stage esophagectomy for carcinoma of the esophagus in a tertiary care cancer centre.

e16078 Background: This study is to evaluate the safety and technical feasibility of total robot-assisted three-stage esophagectomy in terms of: Completeness of surgery, margin status, lymph nodes harvested, learning curve, docking time and total operating time, and associated morbidity and mortality. Methods: It is a prospective non-randomised study from Nov 2016 to Nov 2022 with a total of 168 patients. Inclusion criteria: Histologically proven squamous cell carcinoma, adenocarcinoma of the intrathoracic esophagus surgically resectable (T1-3,N0 -1,M0); ECOG performance status: 0,1 or 2. Exclusion criteria: Carcinoma of cervical esophagus; patients unfit for general anesthesia; stage IV disease. Results: In a total of 168 patients, 52% had Squamous cell carcinoma and 48% had Adenocarcinoma; 8% had upper thoracic, 44.5% mid thoracic and 47% lower thoracic lesions. Mean docking time of 33 mins and mean operating time of 321 min. Average hospital stay of 7 days with average of 44 lymph nodes retrieved and mean blood loss of 280 ml. Intra operative complications of RLN injury in 2%, Thoracic duct injury in 1.6%, and Azygous vein injury in 1%.Post operative complications such as delayed gastric emptying in 3.5%, anastomotic leak in 2.9%, pleural effusion in 2.4%, wound infection in 0.6% and re-exploration in 1.7%. Conclusions: Robotic-assisted esophagectomy has its own unique benefits of very low conversion rates, short learning curve, good quality lymphadenectomy in supra-azygous and bilateral recurrent laryngeal nerve area, less painful with faster recovery even in aged patients with significant co-morbidities. Future RCT may confirm the lower incidence of major complications, and similar OS and DFS compared to open approaches.[Table: see text][Table: see text]

The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy.

Total pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis. From May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed. The mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups. The mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients.

Deeper endotracheal intubation offers generous views for endoscopic submucosal dissection of cervical esophageal carcinoma.

The efficacy and safety of endoscopic submucosal dissection (ESD) for treating cervical esophageal carcinoma (CEC) are well recognized [1] [2]. However, performing ESD in the cervical esophagus remains challenging due to upper sphincter contraction and endotracheal intubation balloon compression. Herein, a deeper endotracheal intubation was applied to tackle this technical difficulty.

Clinical Outcomes of Definitive Chemoradiotherapy for Cervical Esophageal Cancer.

To investigate the clinical outcomes of concurrent chemoradiotherapy (CCRT) in patients with cervical esophageal carcinoma and analyze the prognostic factors. Thirty-nine patients with cervical esophageal carcinoma were retrospectively identified among consecutive patients who received CCRT between November 2009 and September 2019 at our institution. The patients were treated by intensity-modulated radiation therapy (N=13) or three-dimensional conformal radiotherapy (N=26). The median follow-up period was 35 months (range=2-158 months). There were 32 men and 7 women with a median age of 66 years (range=50-83 years). Clinical stages were I in 6 patients, II in 4, III in 19, and IV in 10. Hypopharyngeal invasion was noted in 8 patients. The initial treatment responses were evaluated 3-6 weeks after the final session of CCRT: a complete response (CR) in 24 patients, a partial response (PR) in 13, and stable disease (SD) in 2. Two- and 5-year overall survival (OS) rates were 73.8 and 59.4%, respectively. Two- and 5-year progression-free survival (PFS) rates were 57.8 and 48.0%, respectively. A univariate analysis identified the initial treatment response (CR or non-CR) as a significant factor for OS (p=0.0002) and PFS (p=0.0026). The CR rate was 81.0% in patients with T1-3 and 33.3% in those with T4 (p=0.0038). Patients with cervical esophageal carcinoma in Nagasaki University Hospital in Japan achieved superior outcomes compared with previous studies. CR rate was higher in patients with T1-3 and correlated with better OS.

Reply to Letter to the Editor regarding "Oncological outcomes of squamous cell carcinoma of the cervical esophagus treated with definitive (chemo-)radiotherapy: a systematic review and meta-analysis".

In a previous study, we performed a meta-analysis of the oncological outcomes of patients suffering from cervical esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. Further analysis was performed, and a random effect modeling showed a pooled local-regional failure rate of 41.4% (95% CI 32.2-50.8), and a pooled distant failure rate of 21.6% (95% CI 17.0-26.5). The included studies used a median radiotherapy (RT) dose of 61.2Gy (95% CI 60.0-62.0, range 56.0-66.0), but we measured a non-significant impact of the RT dose on the pooled overall survival (OS), suggesting that an increased RT dose might not be related to an improved OS (p = 0.23). Further research should be conducted to define predictors and prognostic categories that may select the best treatment option for each patient.

Treatment and Outcomes of Proximal Esophageal Squamous Cell Carcinoma.

This study evaluated the treatment of proximal (cervical or upper thoracic) esophageal squamous cell carcinoma (SCC), for which chemoradiation is the recommended therapy. Treatment and outcomes of patients with cT1-3N0-1M0 proximal esophageal SCC in the National Cancer Database between 2004 and 2016 was evaluated using logistic regression, Kaplan-Meier analysis, and propensity-score matching. Therapy of 2159 patients was chemoradiation (n=1500, 69.5%), no treatment (n=205, 9.5%), surgery (n=203, 9.4%), radiation alone (n=190, 8.8%), and chemotherapy alone (n=61, 2.8%). Factors associated with definitive therapy with either chemoradiation or surgery were younger age, non-Black race, being insured, cervical tumor location, clinical T2 and T3 stage, clinical nodal involvement, and treatment at a research/academic program. Five-year survival was significantly better in patients treated with definitive therapy than patients not treated definitively (34.0% vs. 13.3%, p<0.001). In multivariable survival analysis, receiving definitive therapy (hazard ratio [HR] 0.39, p=0.017) was associated with improved survival, while increasing age, male sex, clinical T3 stage, positive clinical nodal involvement, and increasing Charlson Comorbidity Index were associated with worse survival. Esophagectomy was not associated with improved survival in multivariable analysis of the definitive therapy cohort (HR 0.84, p=0.08) or propensity matched analysis. However, the pathologic complete response was only 33.3% (40/120) for patients who did have an esophagectomy after chemoradiation. This national analysis supports definitive chemoradiation for not only cervical but also proximal thoracic esophageal SCC. Routine surgery does not appear to be necessary but may have a role in patients with residual disease after chemoradiation.

Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

The Treatment Outcomes of Patients with Cervical Esophageal Carcinoma Undergoing Definitive Chemoradiotherapy: A Multi-Institutional Analysis TROD 01-005

<h3>Purpose/Objective(s)</h3> To investigate the clinical outcomes of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy (CRT). <h3>Materials/Methods</h3> The clinical data of 180 patients received concurrent CRT between April 2005 and September 2021 at 17 institutions were retrospectively analyzed. All patients were treated with curative intent CRT. Only patients treated with definitive intent, and squamous histology were analyzed. Patients who were treated with adjuvant or neoadjuvant setting or adenocarcinoma histology were excluded. The primary endpoint was LC, and the secondary endpoints were PFS and OS. <h3>Results</h3> Median age was 56 years (range; 26-87 years). Mean tumor size was 4.9 ± 2.1 cm. Majority of patients (60.6%) are female, had extensive T stage (78.9%), and regional lymph node metastasis (60.6%). Median fraction and total radiation doses were 2 Gy (range, 1.8-2.3 Gy) and 60 Gy (45-72 Gy), respectively delivered in median 30 fractions (range, 23-38 fr). Thirty-six patients (20%) were treated with 3-D conformal radiotherapy (RT) and 144 patients (80%) received intensity modulated RT (IMRT). Majority of the patients (49.4%) received concurrent cisplatin-based chemotherapy with a median 5 cycles (range, 1-8). Median follow-up was 20.7 months (range, 2.4-155.2 months). The 2-year OS and PFS rates were 58.7% and 47%, respectively. The 2-year LC was 69.5%. In univariate analysis ECOG performance score (p:0.01) and treatment response (p<0.001) were significant prognostic factors for OS and PFS. In multivariate analysis ECOG score 2 (HR=1.94, 95%CI, 1.18-3.18, p=0.009) and incomplete treatment response (HR=4.42, 95%CI, 2.80-6.99, p<0.001) were independent predictors for worse OS. In multivariate analysis ECOG score 2 (HR=1.73, 95%CI, 1.0.7-3.79, p=0.003) and incomplete treatment response (HR=4.42, 95%CI, 2.88-6.74, p<0.001) were independent predictors for worse PFS. <h3>Conclusion</h3> We found that CRT is a safe and effective treatment modality in patients with cervical esophageal carcinoma. The treatment response and patient performance status were predictive for survival. Further prospective studies with larger cohorts are warranted to confirm our findings.

347. DEFINITIVE CHEMORADIOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL (DCF-RT) FOR ADVANCED CERVICAL ESOPHAGEAL CANCER

Abstract Recently, the selection rate of definitive chemoradiotherapy (CRT) as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) has increased to preserve the larynx. However, many things about the regimen, irradiation field, or which is better treatment have not been determined. We have started definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical esophageal squamous cell carcinoma. We evaluated 20 advanced cervical ESCC patients (clinical stage II–IV, including T4b and/or M1 lymph node) in our department who received DCF-RT as the first-line treatment between December 2010 and August 2021. 16 males and 4 females. The pretreatment clinical stage included one stage II, five stage III, six stage IVa, and eight stage IVb cases (including 10 with T4b and 8 with M1 lymph node. Grade 3 or more adverse events included leucopenia (95%), neutropenia (90%), febrile neutropenia (55%). We attained CR in 17 patients (85%), SD in 2 patients, and PD in 1 patient. Of 17 patients with CR, 8 experienced recurrence and 9 continued exhibiting CR. Two patients who underwent salvage surgery. While the 2−/3-year overall survival rate was 60.2%/46.4%, the 2−/3-year recurrent-free survival rate was 51.4%/45.7%, respectively. DCF-RT for advanced cervical ESCC could be completed by the careful administration, and although a strong blood toxicity might occur, a favorable prognosis can be obtained with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.