Esophagus cancer

Introduction

Esophageal cancer (EC) is the sixth leading cause of cancer death worldwide and is responsible for 400,000 new cases (4.9% of all cancers) cancer deaths annually. The incidence of EC differs greatly according to geographic region, with the highest incidence in Asian and Middle Eastern countries. In most Western countries, such as the United States, adenocarcinoma has eclipsed squamous cell carcinoma as the predominant histologic type, and it usually afflicts white men. In contrast, squamous cell carcinoma is mostly related to smoking and alcohol consumption in Asia and Middle Eastern countries. Adenocarcinoma is also closely linked with obesity, which, with the associated reflux esophagitis and Barrett preneoplasia, are becoming epidemic in the West and in developed countries.

Historically, the previous standard treatment approach, surgical resection with or without adjuvant therapy, produced cure rates of only about 20%; thus, the addition of preoperative chemoradiation is increasingly being adopted, given the evidence that this approach improves overall survival (OS) relative to surgery alone. The largest of the randomized trials performed in the modern era was a phase III randomized study from a Dutch group, in which 366 evaluable patients were randomized to surgery versus preoperative chemoradiation to 41.4 Gy with carboplatin and paclitaxel. The preoperative chemoradiation substantially improved the median OS time (49.4 months vs. 24.0 months in the surgery-only group). The pathologic complete response rate in the preoperative chemoradiation group was 29% and was higher among patients with squamous cell carcinoma than those with adenocarcinoma (49% vs. 23%; P = .008), which also translated to improved OS from chemoradiation relative to surgery alone for squamous tumors relative to adenocarcinomas (adjusted hazard ratio: 0.42 [95% confidence interval (CI): 0.23–0.79] vs. 0.74 [95% CI: 0.54–1.02]).

Because of the location of the esophagus, mid- and distal esophageal tumors span posteriorly across the heart and are in very close proximity to the left atrium and anteriorly to the thoracic vertebrae. Proton beam therapy (PBT) is therefore ideal for the treatment of EC, given the tight dose conformality it provides. Comparisons of PBT with three-dimensional (3D) conformal therapy and intensity-modulated (photon) radiation therapy (IMRT) are described in further detail later in this chapter. The following sections describe procedures for treatment simulation, radiation dose and fractionation, target delineation, and treatment verification when using PBT for esophageal tumors, followed by descriptions of aspects of treatment planning that are specific to the two major types of PBT: passive scattering or intensity-modulated proton therapy (IMPT).

Treatment simulation

For treatment simulation, patients with cervical tumors should be supine and immobilized with a five-point mask, with indexed head, neck, and shoulder stabilization. Patients with thoracic or gastroesophageal junction tumors are also positioned supine and immobilized with the use of an indexed upper Vac-Loc/alpha cradle, with both arms up; potential deflation of the cradle must be monitored. The isocenter is placed at the carina. Respiratory motion should be assessed by four-dimensional (4D) scanning, as the esophagus and surrounding structures can move substantially with respiratory motion, particularly at the gastroesophageal junction. Simulation should ideally take place with the patient’s arms above their head to maximize the number of beam arrangements that can be used. To improve reproducibility, patients should be advised to consume nothing by mouth for at least 3 hours before the simulation and before each daily treatment.

Radiation dose and fractionation, target delineation, and treatment verification

A summary of these topics, discussed in further detail below, is provided in Table 17.1 .