SAN ANTONIO-Targeting radiotherapy to the primary tumor in squamous cell carcinoma of the esophagus is relatively straightforward, but there is some controversy about whether to use targeted involved-field radiation or a more regional approach with elective nodal radiation for the surrounding nodes.
Elective nodal irradiation is most commonly used for esophageal cancer but the related side effects and toxicity have been criticized.
New research from China, however, reported here at the American Society for Radiation Oncology Annual Meeting, suggests that involved-field irradiation may be just as effective but less toxic than elective nodal irradiation (Abstract 7).
Preliminary Results
Preliminary results of the randomized CSWOG-RTOG 002 study with 110 patients, which compared involved-field radiation with elective nodal irradiation for locally advanced esophageal cancer were presented by Tao Li, MD, PhD, Vice Chairman of the Department of Radiation Oncology at Sichuan Cancer Hospital and Institute in China. There was no statistically significant difference in the rates of locoregional lymph node recurrence, distant failure, or overall survival between the two modalities, but there was a significant difference in toxicity.
A total of 54 patients received involved-field radiation and 56 had elective nodal irradiation. All patients were treated with concurrent chemoradiotherapy of docetaxel (at 75 mg/m2 on day one) and cisplatin (at 25 mg/m2 on days 1-3) every 21 days for two to four cycles.
Radiotherapy was given by image-guided radiation therapy in once-daily fractions of 1.8 to 2 Gy, to a total dose of 60 to 66 Gy to the gross tumor volume and 50 to 54 Gy to the clinical target volume.
Li reported that at a median follow-up of 20 months, there was no difference in distant failure rates between the two study arms: 13 percent for involved-field versus 12.5 percent for elective nodal irradiation.
The locoregional lymph node recurrence rate at 20 months was 20 percent for involved-field radiation versus 18 percent for elective nodal radiation.
The two groups of patients had similar overall survival rates: the one-year rate was 88 percent for the involved-field group versus 89 percent for the elective nodal group; two-year overall survival rates were 56 and 64 percent, respectively.
And at 20 months, 13 percent of patients receiving involved-field radiation had experienced radiation pneumonitis versus 27 percent for those undergoing elective nodal irradiation; the rates of radiation esophagitis were 20.4 and 37.5 percent, respectively.
Relevant in U.S.?
The Discussant for the paper, Brian G. Czito, MD, Associate Professor of Radiation Oncology at Duke Cancer Institute, noted that although esophageal cancer makes up only approximately one percent of all cancers diagnosed in the United States, it is far more prevalent in China, with esophageal squamous cell carcinoma the most common type. He advised caution regarding the applicability of the data to a Western population, where adenocarcinoma is much more prevalent.
Explaining the background of the study, Czito said: "Definitive treatment of combined modality therapy for squamous cell carcinoma of the esophagus is fraught with high toxicity rates as well as high rates of local regional failure-in the neighborhood of 50 percent-despite elective nodal irradiation. Efforts to define the target and the scale of elective nodal treatment are important clinical questions in this disease."
He added that lymphatic spread in esophageal cancer is common-for example, an autopsy series showed an incidence of approximately 70 percent-due to the fact that the lymphatics of the esophagus are extensive, longitudinal, and interconnecting.
Conventional imaging approaches can miss these metastatic nodes, which are most often smaller than one centimeter. "Most metastatic nodes are going to be microscopic and not macroscopic," Czito said.
Fortunately, though, there are patterns of spread in esophageal squamous cell carcinoma, and these are highly contingent upon the location of the tumor within the esophagus. Most nodes are immediate or adjacent to the primary tumor.
"But no matter how large the radiation fields, there are always going to be patients who have disease outside of the field.
Czito said that proponents of the involved fields, as tested in this trial, rationalize that:
* An involved field is associated with decreased rates of toxicity;
* Isolated out-of-field nodal failure rates are uncommon;
* Distant disease and in-field failures are the dominant nodes of relapse; and
* Micrometastatic disease can be controlled, either through chemotherapy or even through incidental lower-dose radiation to subclinical disease.
Interim Analysis
Czito reminded the audience that the study is an interim analysis with a relatively small number of patients-110 accrued out of an anticipated 320. "Clearly there is the possibility that the study is underpowered to detect the differences there," he said.
Additionally there is short follow-up. He said it is also possible that once more distant nodes are involved-"the so-called 'horse out of the barn,' meaning that cure is unlikely"-metastases are likely, and reliance on an extended field or elective nodal irradiation may not have much impact on the overall outcome of the disease.
There are notable differences in this trial compared with what is practiced in the United States, Czito noted. For example, the doses of radiation were higher-50 to 54 Gy to the planning treatment volume, and up to 60 Gy to the gross tumor volume.
And local failure rates were significantly lower than are seen in Radiation Therapy Oncology Group studies, which are consistently 50 percent, even with dose escalation.
"Dr. Li and colleagues are to be congratulated for conducting this very interesting trial of a novel treatment technique to help us better define our esophageal cancer fields, and potentially improve the tolerance of such in this otherwise toxic treatment," Czito concluded. But "further follow-up is necessary; further study is needed before these results can be implemented as definitive therapy."