Neoadjuvant versus adjuvant chemoradiation for stage II-III esophageal squamous cell carcinoma: a single institution experience.

Esophageal cancer is the eighth most common cancer worldwide. It is the fourth most common cause of cancer death in China and esophageal squamous cell carcinoma (ESCC) is the most prevalent histologic type. Many clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation therapy in potentially resectable ESCC; however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. A review of stage II/III thoracic ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Chemotherapy regimen consisted of cisplatin 75 mg/m2 divided into 3 days and fluorouracil 500 mg/m2 on days 1 to 5. The patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy concurrently with radiotherapy (40 Gy in 20 fractions, 5 days/week), and those receiving adjuvant therapy were treated with two cycles of chemotherapy concurrently with radiotherapy (46-50 Gy in 23-25 fractions, 5 days/week). A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year overall survival (OS) rates for the neoadjuvant and adjuvant groups were 39.3 versus 31.5 months, and 53.0%, 45.7% versus 42.9%, 29.7%, respectively (P = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 versus 21.3 months, and 43.4% versus 21.0%, respectively (P = 0.021). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 versus 23.7 months, and 43.0% versus 25.7%, respectively (P = 0.085). The incidence of perioperative and postoperative complications was comparable between the two groups (P > 0.05). For patients with resectable stage II/III ESCC, neoadjuvant chemoradiation does not increase postoperative complications and is associated with a trend toward better OS when compared to adjuvant chemoradiation.

Chen Y ，Hao D ，Wu X ，Xing W ，Yang Y ，He C ，Wang W ，Liu J ，Wang J ... -  《-》

Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.

Matsuda S ，Tsubosa Y ，Sato H ，Takebayashi K ，Kawamorita K ，Mori K ，Niihara M ，Tsushima T ，Yokota T ，Onozawa Y ，Yasui H ，Takeuchi H ，Kitagawa Y ... -  《-》

A retrospective comparison of neoadjuvant chemoradiotherapy regimens for locally advanced esophageal cancer.

Preoperative chemoradiotherapy (CRT) with carboplatin/paclitaxel has been shown to increase survival in patients with esophageal cancer, including gastroesophageal junction (GE) junction cancer, over surgery alone; however, there have been no studies comparing the different neoadjuvant CRT regimens. We retrospectively evaluated the long-term results of trimodality therapy for patients with locally advanced esophageal cancer treated on several chemotherapy regimens. Between 1999 and 2014, 215 patients with locally advanced esophageal cancer underwent neoadjuvant CRT followed by surgical resection. The median age was 62 years (range 21-84), 80.5% were men and 86% had adenocarcinoma. The following chemotherapy regimens were administered: cisplatin/5FU (14.9%), cisplatin/irinotecan (35.8%), carboplatin/paclitaxel (35.8%), and other (9.7%). The majority of patients (92.1%) received a radiation dose of 50.4 Gy. Predictors of toxicities and surgical complications were assessed using logistic regression. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and proportional hazards regression was used to model time-to-event outcomes. The median follow-up among surviving patients was 4.1 years (range 0.4,13). The median OS was 3.0 years from time of diagnosis and OS was 36.8% at 5 years. RFS was 34.9% at 5 years. After neoadjuvant CRT, 34.7% of patients achieved a pathologic complete response including 60.7% of squamous cell carcinoma patients and 18.4% of adenocarcinoma patients (P < 0.001) and 66% were downstaged. Of the variables examined, pathologic stage, preoperative baseline cardiac comorbidity, postoperative cardiac or pulmonary complications, and chemotherapy regimen were associated with OS. Using cisplatin and 5FU as the reference regimen, patients treated with carboplatin/paclitaxel had significantly improved OS (HR = 0.47, P = 0.017 after adjusting for surgery type, radiation modality, baseline cardiac comorbidity, and preoperative stage) with 5-year OS rate of 66%. The most common surgical complications were cardiac in 61 patients (28.5%) and pulmonary in 52 patients (24.3%). Cardiac complications were associated with age (OR 1.05, P = 0.007) and cardiac comorbidity (OR 2.6, P = 0.02) and pulmonary complications with female gender (OR 3.98, P < 0.001). Forty-four patients (20.5%) required readmission within 30 days of discharge, and readmission was associated with cardiac comorbidity (OR 2.7, P = 0.017). Three patients died within 30 days of surgery. We observed an association between neoadjuvant carboplatin/paclitaxel and improved overall survival that requires confirmation in a prospective randomized trial.

Sanford NN ，Catalano PJ ，Enzinger PC ，King BL ，Bueno R ，Martin NE ，Hong TS ，Wo JY ，Mamon HJ ... -  《-》

CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell

Tang H ，Tan L ，Shen Y ，Wang H ，Lin M ，Feng M ，Xu S ，Guo W ，Qian C ，Liu T ，Zeng Z ，Hou Y ，Yu Z ，Jiang H ，Li Z ，Chen C ，Lian C ，Du M ，Li H ，Xie D ，Yin J ，Zhao N ，Wang Q ... -  《BMC CANCER》

Prognostic significance of pathological tumor response and residual nodal metastasis in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery.

Oguma J ，Ozawa S ，Koyanagi K ，Kazuno A ，Yamamoto M ，Ninomiya Y ，Yatabe K ... -  《-》