An Open-Label Single-Arm Phase II Study of Treatment with Neoadjuvant S-1 Plus Cisplatin for Clinical Stage III Squamous Cell Carcinoma of the Esophagus.
一项新辅助 S-1 联合顺铂治疗临床 III 期食管鳞状细胞癌的开放标签单臂 II 期研究。
- 作者列表："Kanda M","Koike M","Iwata N","Shimizu D","Tanaka C","Hattori N","Hayashi M","Yamada S","Omae K","Nakayama G","Kodera Y
LESSONS LEARNED:Two courses of neoadjuvant therapy using S-1 plus cisplatin for clinical stage III esophageal squamous cell carcinoma did not achieve expected response rate according to endoscopic evaluation of primary tumors. Subsequent esophagectomy was safely performed. BACKGROUND:In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the need for a more effective regimen. METHODS:A single-arm, open-label phase II trial was conducted to evaluate the safety and efficacy of two courses of neoadjuvant chemotherapy using S-1 plus cisplatin (NAC-SP) for clinical stage III ESCC. The primary endpoint was overall response rate as defined by endoscopic evaluation of primary tumors. RESULTS:We enrolled 26 patients. The completion rate for the two courses of NAC-SP was 61.5%. Grade 3 or higher adverse events were experienced by 38.4% of patients. The treatment response rate according to endoscopic findings, acquired before the second course, was 34.6% and below the expected level (55.0%). The morbidity rate of patients who underwent radical subtotal esophagectomy (96.2%) was 32.0%. Repeat surgery was unnecessary, and surgery-associated deaths did not occur. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 84.6% and 92.2%, respectively. CONCLUSION:We demonstrate safety of NAC-SP, but not its efficacy, for patients with clinical stage III ESCC. Subsequent esophagectomy was safely performed.
经验教训: 根据原发肿瘤的内镜评估，临床III期食管鳞状细胞癌使用S-1 加顺铂的两个疗程的新辅助治疗没有达到预期的反应率。随后的食管切除术是安全的。 背景: 在日本，5-氟尿嘧啶联合顺铂两个疗程后的食管切除术被认为是治疗II或III期食管鳞状细胞癌 (ESCC) 的标准策略。然而，5-氟尿嘧啶联合顺铂对临床III期ESCC的队列没有益处，提示需要更有效的方案。 方法: 一项单组、开放的II期临床试验旨在评价S-1 联合顺铂 (NAC-SP) 新辅助化疗两个疗程的安全性和有效性。对于临床III期ESCC。主要终点是通过内镜评估原发性肿瘤定义的总体缓解率。 结果: 我们入组了 26 例患者。NAC-SP两个疗程的完成率为 61.5%。38.4% 的患者经历了 3 级或更高的不良事件。根据内镜检查结果，第二疗程前获得的治疗应答率为 34.6%，低于预期水平 (55.0%)。根治性食管次全切除术的发病率 (96.2%) 为 32.0%。重复手术是不必要的，手术相关的死亡没有发生。5 年无进展生存期 (PFS) 和总生存期 (OS) 率分别为 84.6% 和 92.2%。 结论: 对于临床III期ESCC患者，我们证明了NAC-SP的安全性，但不是其疗效。随后的食管切除术是安全的。
METHODS:PURPOSE:The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods:A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. RESULTS:With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. CONCLUSION:No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.
METHODS::The radial force of esophageal stents may not completely change during extraction and therefore, the procedure of stent removal may cause tissue damage. The present study reports the manufacture of 2 novel detachable stents, which were designed to reduce tissue damage through their capacity to be taken or fall apart prior to removal and evaluated the supporting properties of these stents and the extent of local mucosal injury during their removal. The stents were manufactured by braiding, heat-setting, coating and connecting. The properties of the stents were evaluated by determining the following parameters: Expansion point, softening point, stent flexibility, radial compression ratio and radial force. A total of 18 rabbits with induced esophageal stricture were randomly assigned to 3 groups as follows: Detachable stent (DS) group, biodegradable stent (BS) group and control group. The stricture rate, complications, survival, degradation and stent removal were observed over 8 weeks. The stents of the DS and BS groups provided a similar supporting effect. The stricture rate, incidence of complications and survival were also similar between the 2 groups, while significant differences were noted between the DS and control groups and between the BS and control groups. In the BS group, the stents were degraded and moved to the stomach within 7 weeks (2 in 6 weeks and 3 in 7 weeks). The debris was extracted using biopsy forceps. In the DS group, all stents were easy to remove and 2 cases exhibited minor hemorrhage. In conclusion, the 2 types of novel detachable stent provided an equally efficient supporting effect in vitro and in vivo and may reduce the incidence of secondary injury during stent removal.
METHODS:BACKGROUND:Immune imbalance and inflammation have been suggested as key factors of Barrett's esophagus (BE) pathway towards adenocarcinoma. The neutrophil-lymphocyte ratio (NLR) indirectly reflects the relation between innate and adaptive immune systems and has been studied in premalignant conditions as a biomarker for cancer diagnosis. Our aim was to investigate if increasing values of NLR correlated with advancing stages of BE progression to dysplasia and neoplasia. METHODS:We retrospectively analyzed data of patients with biopsies reporting BE between 2013 and 2017 and with a complete blood count within 6 months from the endoscopy, as well as patients with esophageal adenocarcinoma (EAC). NLR was calculated as neutrophil count/lymphocyte count. Cases (n = 113) were classified as non-dysplastic BE (NDBE, n = 72), dysplastic BE (DBE, n = 11) and EAC (n = 30). RESULTS:NLR progressively increased across groups (NDBE, 1.92 ± 0.7; DBE, 2.92 ± 1.1; EAC 4.54 ± 2.9), with a significant correlation between its increasing value and the presence of dysplasia or neoplasia (r = 0.53, p 2.27 was able to diagnose EAC with 80% sensitivity and 71% specificity (area under the curve = 0.8). CONCLUSION:NLR correlates with advancing stages of BE progression, a finding that reinforces the role of immune imbalance in EAC carcinogenesis and suggests a possible use of this marker for risk stratification on surveillance strategies.