Currently, to the best of our knowledge, there have not been any studies regarding dosimetric evaluation of IFI for ESCC with 3D-CRT. This study demonstrated that the incidental irradiation dose to high-risk nodal regions is considerable. The incidental irradiation dose in most of the high-risk regions with an EUD less than 40 Gy was significantly associated with the length and location of the esophageal tumor. However, this association did not exist between the length of the PTV located in the abdomen and incidental irradiation dose of region 3&7 of lower-thoracic ESCC. Uncertainty of the stomach anatomy may explain the lack of correlation. Additionally, all high-risk nodal regions likely do not receive high enough incidental irradiation doses in all patients studied, even when the median Dmean or EUD was more than 40 Gy, a typical dose for ENI in most nodal regions. However, it has been reported that worthwhile treatment benefits can be achieved by lower doses (e.g., 10–30 Gy), and that a radiation dose as low as 24 Gy could reduce metastases by 30–50% [12–14].
It is generally accepted that the length of the thoracic esophageal lesion correlates with node metastasis. That is, the longer the thoracic ESCC, the greater the likelihood of lymph node metastasis [4, 5]. In our study, incidental irradiation doses in regions 104 and 106tb-R of upper-thoracic ESCC, 105 and 106rec-L of middle-thoracic ESCC, and region 107 of lower-thoracic ESCC, were significantly associated with esophageal tumor length and location. This may explain why the isolate out-field nodal failure rate was low when employing 3DCRT without intentional elective nodal irradiation.
The isolate out-field nodal failure rate was low and overall survival did not decrease when IFI was used [6, 7, 15, 16]. Zhao et al. reported the results of a prospective study of 3D-CRT in 53 ESCC patients without distant metastases. Only the primary tumor and positive lymph nodes were irradiated in the study. Thirty-nine of the 53 patients (74%) showed treatment failure, but only three patients (8%) developed isolated out-of-field nodal recurrence. Button et al. performed a retrospective study of 145 patients (75% with stage III-IV) of esophageal carcinoma (45% had adenocarcinoma) with conformal RT (50 Gy in 25 fractions). After RT, 85 patients (60%) had evidence of relapse at a median follow-up of 18 months, but only 3 patients (4%) developed relapse in regions adjacent to the RT fields. The low out-field failure maybe due to the incidental irradiation to elective nodal regions. In our study with T1-4N0M0 patients, most high-risk nodal regions receive considerable doses, especially patients with long lesions. In clinical practice, however, more patients were presented with positive lymph node metastasis, in which the incidental irradiation dose to high-risk regions would much higher. Additionally, more high-risk regions would receive considerable doses if metastatic nodes were included in GTV. As a result, we believe that incidental irradiation may play a role in the control of micro-metastasis.
In the study, the prescribed dose was 60Gy/30f by conventional fractionation. This dose considers the discrepancy of tumor radiosensitivity and tolerance of chemoradiotherapy between Western populations and Asian populations, despite the fact that patients do not obtain benefits with a higher dose than 50.4Gy/28f, according to RTOG 94–05 . In our study, the CTV was generated with a 3 cm margin to the GTV. Incidental irradiation to the cranio-caudal direction outside the treatment field should be much lower. However, in the cranio-candal directions, a 3–5 cm margin is usually added to the GTV to generate CTV, and, after radiation therapy, lymph node recurrence at a region 3–5 cm far away from the GTV is not common [6–8, 15, 16]. Literatures also suggested that 3–5 cm margin in the cranio-candal direction can obtained similar results compared with larger margins [1–3].
In summary, our study demonstrated that, in thoracic esophageal carcinoma, involve-field irradiation may deliver considerable incidental dose to elective regions, which will have significant impact on the control of micro-metastasis. If incidental out-field nodal irradiation does control micro-metastasis, when use such modern radiation techniques as stereotactic radiotherapy, intensity modulated radiotherapy, and proton therapy, the omission of ENI should be performed with caution. Furthermore, the incidental irradiation dose is generally related to the conformal level of the plan, which is associated with the treatment technique, number of beams, beam arrangement, and leaf thickness of MLC. However, this study does not have the capability to investigate this question due to the relative uniform consideration of technical factors. Moreover, future clinical studies should be performed to evaluate the feasibility of IFI in the radiation therapy of esophageal squamous carcinoma.