Abstract
Abstract Patients with different ethnic and genetic backgrounds may respond differently to specific anticancer therapies. The present study aimed to assess whether patients with esophageal squamous cell carcinoma (ESCC) who are treated with neoadjuvant chemoradiotherapy (nCRT) according to the CROSS regimen in East Asia have an inferior response compared to patients treated in Western Europe. Patients with ESCC who completed ≥80% of nCRT according to CROSS (five weekly cycles of carboplatin [AUC of 2 mg/mL/min] and paclitaxel [50 mg/m2] with concurrent 41.4 Gy radiotherapy in 23 daily fractions of 1.8 Gy) followed by esophagectomy between June 2012 and April 2020 were identified from Asian and Dutch databases. Primary endpoint was pathologically complete response (pCR), defined as ypT0N0. Asian and Dutch patients were compared with nearest-neighbor propensity score matching, adjusting for confounding factors: gender, Charlson comorbidity index, tumor location, cT and cN stage, interval from start of nCRT to surgery, and number of resected lymph nodes. In total, 839 patients were included (Asian: 175, Dutch: 664). After matching, 154 remained in each group. Confounding factors were all significantly different before matching and 26% in the Asian versus 42% in the Dutch cohort had a pCR (p<0.001), which became 27% versus 42% after matching (p=0.008), respectively. Both ypT and ypN stage were significantly higher in the Asian cohort. R0 resection rate was comparable (Asian: 92% vs. Dutch: 95% resp., p=0.29). Asian patients more often had a cervical anastomosis (p=0.001) and less complications including pulmonary complications (21%-38%, p=0.002), chyle leakage (2%-10%, p=0.006) and anastomotic leakage (10%-21% resp., p=0.02). The present study shows that after adjusting for patient and tumor characteristics, East Asian patients with ESCC have a poorer response to nCRT according to the CROSS regimen than Western European patients. The poorer response did not seem to have a negative effect on surgical outcome. Future studies investigating anticancer therapy for esophageal cancer should take into account ethnic and genetic differences in response to these regimens.
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