Phase I study of integrating PET/CT and dose-escalated intensity modulated radiation therapy using a simultaneous integrated boost technique for thoracic esophageal cancer

Background: Esophageal cancer has a poor prognosis because most patients have locally advanced disease upon presentation, and are therefore not suitable for upfront surgery. Modern radiation therapy techniques using intensity modulated radiation therapy (IMRT) combined with a novel imaging technique using integrated positron emission tomography and computed tomography (PET/CT) may help radiation oncologists increase radiation dose to the tumor and may improve tumor response.

Objective: The primary aim was to analyze the toxicity of dose-escalated IMRT using a simultaneous integrated boost (SIB) technique and concurrent chemotherapy in esophageal cancer patients using PET/CT as a guide for target delineation. Secondary endpoints were to evaluate response rate, overall survival, and event-free survival rates.

Method: Seventeen consecutive patients with locally advanced carcinoma of the esophagus were treated with preoperative concurrent chemoradiation that consisted of IMRT 64 Gy in 30 fractions (SIB technique), together with two cycles of cisplatin (80 mg/m², day 1 and 29) and 5-fluorouracil (1000 mg/m²/d, days 1-4 and 29-32). Baseline PET/CT was used for staging and target delineation. After complete chemoradiation for 3 months, PET/CT was repeated and the patients were evaluated for esophagectomy. Treatment toxicities were collected. Baseline and 3-month postchemoradiation PET/CT imaging were analyzed and correlated with the pathological findings.

Result: The median follow-up time was 12 months. All 17 patients had squamous cell carcinoma of thoracic esophageal cancer and were treated with chemoradiation. The most common acute ≥grade 3 adverse effects were leucopenia (58.8) and vomiting (23.5%), respectively. Acute ≥grade 3 cardiotoxicities and pulmonary toxicities were observed in 5.9% and 11.7% of the patients, respectively. One patient (5.9%) died from an esophagopericardial fistula. Seven patients underwent esophagectomy after chemoradiation. A pathologic complete remission was achieved in 4 patients (57.1% of the surgical group or 23.5% of the entire group). The overall 1-year survival and event free survival rates for the entire group of patients were 87% and 59%, respectively. There was a statistically significant difference in the overall 1-year survival between surgical and nonsurgical groups (overall 1-year survival, 100% versus 74%, respectively, p = 0.037). In contrast, there was no significant difference in 1-year event-free survival between groups (1-year event-free survival, 72% versus 56%, p = 0.085). Applying the average absolute reduction and percentage reduction of SUV_max in these patients, PET/ CT could not predict the pathologic response.

Conclusion: Integrating PET/CT for dose-escalated IMRT in esophageal cancer patients showed acceptable toxicities and promising overall survival, especially when followed by surgery.