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Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Cancer

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Key Points

  • Neoadjuvant chemoradiotherapy followed by surgery significantly improved survival over surgery alone.
  • Grade 3 or 4 hematologic toxicity was common in the chemoradiotherapy group.

In a Chinese phase III trial reported in the Journal of Clinical Oncology, Yang et al found that adding neoadjuvant chemoradiotherapy to surgery improved survival in locally advanced squamous cell carcinoma of the esophagus.

Study Details

In the open-label trial, 451 patients with potentially resectable thoracic disease clinically staged as T1-4, N1, M0 or T4, N0, M0 were randomized between June 2007 and December 2014 to receive neoadjuvant chemoradiation followed by esophagectomy (n = 224) or surgery alone (n = 227). Chemoradiotherapy consisted of vinorelbine at 25 mg/m2 on days 1 and 8 and cisplatin at 75 mg/m2 on day 1 or 25 mg/m2 on days 1 to 4 every 3 weeks for 2 cycles, as well as a radiation dose of 40.0 Gy in 20 fractions of 2.0 Gy on 5 days per week.

The primary endpoint was overall survival in the intent-to-treat population.

Survival and Adverse Events

A total of 17% of patients in the chemoradiotherapy group did not undergo surgery. The pathologic complete response rate was 43.2% in the chemoradiotherapy group. The R0 resection rate was 98.4% in patients in the chemoradiotherapy group undergoing surgery vs 91.2% in the surgery group (P = .002).

Median overall survival was 100.1 months in the chemoradiotherapy group vs 66.5 months in the surgery group (hazard ratio [HR] = 0.71, P = .025). Overall survival rates were 90.0% vs 86.2% at 1 year, 75.1% vs 72.5% at 2 years, and 69.1% vs 58.9% at 3 years. Among the 389 patients with R0 resection, median disease-free survival was 100.1 months vs 41.7 months (HR = 0.58, P < .001).

Grade 3 or 4 hematologic toxicity occurred in 54% of the chemoradiotherapy group, with the most common being leukopenia (49%) and neutropenia (46%). Grade 3 or 4 nonhematologic toxicity occurred in 7% of chemoradiotherapy recipients. The incidence of postoperative complications was similar between the 2 groups, except for a significantly higher incidence of arrhythmia in the chemoradiotherapy group (13% vs 4.0%, P = .001). Peritreatment mortality was 2.2% in the chemoradiotherapy group vs 0.4% in the surgery group (P = .212).

The investigators concluded, “This trial shows that [neoadjuvant chemoradiotherapy] plus surgery improves survival over surgery alone among patients with locally advanced [esophageal squamous cell carcinoma], with acceptable and manageable adverse events.”

The study was supported by grants from the Health Ministry of China, Sun Yat-sen University Clinical Research 5010 Program, National Science Foundation of China, and others.

Jianhua Fu, MD, PhD, of the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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