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Irradiation Techniques

For patients who receive postoperative EBRT following surgical resection or exploratory laparotomy, the irradiation field should include unresected or residual tumor or the tumor bed plus major nodal regions. The pattern of tumor bed and nodal failures in the reopera-tive series from the University of Minnesota is demonstrated in Figure 75-4A in conjunction with an idealized, shaped AP-PA irradiation portal that incorporates the areas of local-regional relapse. 13,123 The tumor bed and nodal volumes are reconstructed with the aid of preoperative and postoperative imaging studies and surgical clip placement. In Figure 75-4B, the idealized AP-PA field is superimposed on the organs and structures that define irradiation tolerance. For individual patients, the idealized field needs to be modified depending on the surgical or pathological extent of disease (based on primary site and TN extent of disease) and the adjacency of tolerance organs and structures.

The relative risk of nodal metastases at a specific nodal location is dependent on both the site of origin of the primary tumor and other factors including width and depth of invasion of the gastric wall. Tumors that originate in the proximal portion of the stomach and the GEJ have a higher propensity to spread to nodes in the mediastinum and pericardial region but a lower likelihood of involvement of nodes in the region of the gastric antrum, periduodenal area, and porta hepatis. Tumors that originate in the body of the stomach can spread to all nodal sites, but have the highest likelihood of spreading to nodes along the greater and lesser curvature, near the location of the primary tumor mass. Tumors that originate in the distal stomach have a high likelihood of spread to the periduodenal, peripancreatic, and porta hepatis nodes but a lower likelihood of spread to nodes near the cardia of the stomach, the periesophageal and mediastinal nodes, or splenic hilar nodes. 260 Any tumor originating in the stomach has a high propensity to spread to nodes along the greater and lesser curvature, although they are most likely to spread to those sites in close anatomic proximity to the primary tumor mass.

With preoperative or primary chemoradiation for GEJ or proximal gastric cancers, because of the risk of submucosal or subserosal lymphatic spread, a > 5-cm margin of uninvolved esophagus/proximal stomach should be included proximally, and the distal/lateral field extent should include a > 5-cm margin of uninvolved stomach (E-Fig. 75-4; Figs. 75-5 and 75-6). If the lesion extends beyond the gastric/ GEJ wall, a major portion of the left hemidiaphragm should be included. Cerrobend blocks or multi-leaf collimators should be used to decrease the volume of irradiated heart and lung, when technically feasible. Preoperative EBRT fields can usually be much more conservative than postoperative fields with regard to both heart and lung volumes, and are preferred, if preoperative imaging and EUS demonstrate indications for preoperative adjuvant treatment. IMRT may improve dose distribution, especially relative to the heart, when compared with three-dimensional (3D) conformal techniques for patients with GEJ cancers treated with preoperative chemoradiation (see Fig. 75-7), but there is uncertainty whether this will improve short-term or long-term treatment tolerance.

With postoperative irradiation of GEJ cancers, the irradiation field may include the anastomotic site and some or all of the remaining stomach. Postoperative fields are larger than preoperative fields unless an involved field approach is chosen for select T3N0 patients.


Dose-Limiting Organs/Structures

Dose-limiting organs and structures in the upper abdomen are numerous (stomach, small intestine, liver, kidneys, and spinal cord). With properly shaped fields, doses of 45 to 50.4 Gy in 1.8- to 2.0-Gy fractions can be delivered to stomach and small intestine with a 5% or less risk of severe toxicity. 201 In most patients, a portion of both kidneys will be within the treatment field, but at least two-thirds to three-fourths of one kidney should be excluded (can include entirety of both kidneys to the level of 20 Gy if necessary). For patients with GEJ or proximal to midgastric cancers (E-Fig 75-4 and Fig. 75-5), one-half to two-thirds of the left kidney can often be spared as a result of accurate field definition, which is aided by pre- and postoperative imaging studies and clip placement. The pancreaticoduodenal nodes can be included, if indicated, while sparing 75% to 90% of the right kidney. However, for distal gastric lesions with narrow or positive duodenal resection margins, the duodenal circumference may need to be included as target volume (Fig. 75-6). In such instances, 50% or more of the right kidney is within the field, and two-thirds to three-fourths of the left kidney should be spared. Chronic renal problems are infrequent when these techniques are used. 181,189,190,202


Multifield Irradiation Techniques

Sophisticated conformal irradiation techniques based on CT-based planning should be used routinely for optimal sparing of normal organs and structures (heart, lung, kidneys, spinal cord). This includes 3D conformal techniques and intensity-modulated radiation therapy (IMRT).

More routine use of multiple field techniques should be considered even for postoperative irradiation, when preoperative imaging exists to allow accurate reconstruction of target volumes (see E-Fig. 75-4, Figs. 75-5 and 75-6). Single-institution data suggest that multiple field arrangements may produce less toxicity. 185 When patients are treated preoperatively, paired lateral fields are usually combined with AP-PA fields to achieve improved dose homogeneity (see Fig. 75-5). Dependent on the posterior extent of the gastric fundus, either oblique or more routine lateral portals can be used to deliver a 10- to 20-Gy component of irradiation to spare the spinal cord or kidney. When lateral fields are used, liver and kidney tolerance limits the use of lateral fields to 20 Gy or less for patients with gastric cancer; for patients with GEJ cancers, the contribution from lateral fields would preferably be limited to 10 to 15 Gy because of lung tolerance.

With the wide availability of 3D conformal treatment-planning systems based on CT imaging, it may be possible to target more accurately the high-risk volume and to use unconventional field arrangements and/or IMRT 203-206 to produce superior dose distribu- tions. To accomplish this without marginal misses, it will be necessary to both carefully define and encompass the various target volumes, because use of oblique or noncoplanar beams could exclude target volumes that would be included in AP-PA fields or nonoblique four- field techniques (AP-PA and lateral). The extent of disease identified on diagnostic endoscopy and EUS and PET/CT should be carefully incorporated into target definition and field design.

When treating patients with distal esophageal or GEJ cancers, irradiation dose to the heart and lung is of particular concern. This is especially true in the neoadjuvant setting because of the risks of perioperative morbidity. Wang et al. found that the volume of lung spared from doses ≥ 5 Gy (V5) was the only independent predictor of perioperative pulmonary complications. 207 Because IMRT may result in increased volume of lung exposed to low doses, it has not gained widespread acceptance over standard four-field conformal treatment design. Care must be taken when choosing beam angles for IMRT to minimize lung V5. However, at Mayo Clinic in Arizona, a retrospective review demonstrated a decrease in lung and heart doses in patients treated with IMRT compared with 3D conformal techniques. 205 This preliminary experience with IMRT has not appeared to compromise early clinical outcomes with respect to disease control or treatment tolerance. At a median follow-up of 27 months, 2-year OS was 55%. In addition, even with the increased use of minimally invasive surgery, there has been no evidence of excessive perioperative complications. 208 The dosimetric improvements of IMRT with regard to the heart may be most significant for reducing long-term cardiac toxicity, which will require longer follow-up of surviving patients in order to detect the full clinical benefits. Hybrid IMRT and conformal plans may also be used to improve target conformality while minimizing the dose to the lungs. 206 Figure 75-7 demonstrates a hybrid IMRT preoperative irradiation treatment plan for a typical GEJ cancer patient.

Acceptable treatment plans can be achieved with either 3D conformal or IMRT planning techniques. The varying length of esophagus required to be treated in patients with distal esophageal and GEJ cancers requires individualization of treatment planning.


Idealized Treatment Field Guidelines

  Guidelines for defining the clinical target volume for postoperative radiation fields have been developed by Tepper and Gunderson based on location and extent of the primary tumor (T category) and location and extent of known nodal involvement (N category). 189,190

Table 75-8 presents general guidelines on the impact of T and N categories on inclusion of the remaining stomach (gastric remnant), tumor bed, and nodal sites, and Tables 75-9 and 75-10 present treatment guidelines based on TN stage for two of the four primary sites (esophagogastric junction, proximal, mid, and distal stomach). In general, for individuals with node-positive disease, there should be wide coverage of tumor bed, remaining stomach, resection margins, and nodal drainage regions. For node-negative disease, if there is a good surgical resection with pathological evaluation of at least 10 to 15 nodes, and there are wide surgical margins on the primary tumor (at least 5 cm), treatment of the nodal beds is optional. Treatment of the remaining stomach should depend on a balance of the probable normal tissue morbidity and the perceived risk of local relapse in the residual stomach.