The 7th Joint Session between JDDW-KDDW-TDDW2(JDDW)
Thu. November 2nd   14:00 - 17:00   Room 9: Portopia Hotel Main Building Kairaku 3
JKT2-1
 Neoadjuvant chemotherapy and conversion surgery for EGJ adenocarcinoma
Yu Imamura1, Keisho Chin2, Masayuki Watanabe1
1Department of Esophageal Surgery, The Cancer Institute Hospital of JFCR, 2Department of Gastroenterology, The Cancer Institute Hospital of JFCR
Background and Aim: Adenocarcinoma of the esophagogastric junction (EGJ) is an aggressive tumor, and curative resection (R0) rate is not sufficient. It has been unclear whether conversion surgery is beneficial in the patient with initially unresectable tumor. Here, focusing on Siewert type I-II cases who needed thoracic approach, and we report 1) a multicenter phase II study of SOX (S-1+ oxaliplatin) therapy as a NAC, and 2) the clinical indication of conversion surgery.
Methods: 1) cT3/4a and/or cN+ cases with 3cm or longer esophageal invasion was eligible. The primary endpoint was R0 resection rate, and the planned sample size was 50 cases based on an expected R0 resection rate of 85% (at the threshold of 70%), with a one-sided alpha of 0.1 and power of 80%. 2) Among 438 cases with Siewert type I /II tumors who were treated at our institution, 95 patients with initially unresectable tumors were examined.
Results: 1) Fifty patients were enrolled between June 2016 and April 2020. The overall response rate (CR/PR was 0/9, respectively) was 18% (95%CI, 8.6-31.4%). SOX-related grade 3-4 adverse events (AEs) occurred in 6 cases. R0 resection rate was 86.0% (95%CI, 73.3-94.2%). Histopathological examination revealed that grades 3/2/1b/1a/0/not-evaluated was observed in 9/6/8/21/4/2 (due to R2 resection), and pathological complete response rate was 18% (95%CI, 8.6-31.4%). 2) Conversion surgery was successfully performed by transthoracic (N=12) or transhiatal approach (N=5), and remaining 60 cases continued chemotherapy (unresected cases). In conversion cases with thoracic approach (N=12), half of those were treated by chemotherapeutic regimen including Trastuzumab (N=5) or Nivolumab (N=1). Compared to the unresected cases, trastuzumab was frequently administered in conversion cases (conversion 50%, unresected 27%), and conversion cases experienced favorable outcomes [3-yr overall survival (OS) after initial treatment; conversion 81.5% vs. unresected 12.7%, P=0.0002].
Conclusions: Neoadjuvant SOX met the primary endpoint of R0 resection rate 86% (>70%), with acceptable adverse events. Conversion surgery conferred prolonged overall survival in the patient with initially unresectable EGJ adenocarcinoma. HER2 overexpression may be a useful biomarker for conversion surgery.
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