This study elucidated the long-term outcomes and recurrence patterns of IFRT for esophageal carcinoma, focusing on a localized irradiation field that excludes prophylactic areas. Older patients diagnosed with thoracic ESCC, the predominant type in Japan, were included in this study. Although several clinical trials have investigated the outcomes of IFRT for superficial esophageal carcinoma; most excluded specific demographics, such as age above 65 years or a history of cancer treatment or severe comorbidities. Thus, the outcomes of IFRT in older patients with esophageal cancer previously treated for cancer or those with significant comorbidities remain unclear.

In this study, the 5-year OS rates for stage I were 71.7%, and by T-factor, 90.0% for T1a and 65.9% for T1b, which were favorable outcomes. Only one patient experienced Grade 3 late toxicity (pericardial effusion), and except for this one patient, no Grade 3 or higher AEs were observed. In a multicenter clinical study, the 5-year OS rates of patients with stage I ESCC who received definitive CRT and radiotherapy alone were 67.1% and 44.8%, respectively [6]. In the JCOG9708 phase II trial of CRT for stage I resectable ESCC, the 4-year OS rate was 80.5%, and grade 3/4 late radiation-related AEs were observed in 3.8% of patients (grade 3 ischemic heart disease, one; grade 3 dyspnea, two) [13]. The JCOG0502 trial compared surgery and CRT outcomes for stage I (T1bN0M0) ESCC. Although the randomized portion of the trial was terminated midway due to poor case accrual, the 5-year OS rate for CRT was 85.5% (95% CI 78.9–90.1), and grade 3/4 late radiation-related AEs were observed in 10.5% of patients (grade 4, four patients). Thus, CRT was not inferior to surgery based on the OS of patients with T1bN0M0 ESCC. CRT may be a standard treatment modality for T1bN0M0 ESCC, similar to surgery [14]. Additionally, JCOG0508 reported a 5-year OS rate of 90.9% (95% CI 85.6–94.3%) for patients with esophageal carcinoma who underwent diagnostic EMR, followed by selective CRT for stage I ESCC [15]. Morota et al. reported that grade 3/4 late cardiopulmonary toxicities were observed in 11.5–28% of patients following definitive concurrent CRT for esophageal carcinoma [16]. Previous reports have indicated that acute radiation-related AEs are rarely a clinical issue; nonetheless, late AEs are challenging.

As for the radiation field setting, some studies suggested that IFRT can improve patient prognosis [17, 18], whereas others have favored elective nodal irradiation (ENI) over IFRT [19, 20]. The treatment strategies for older adults represent an important focus of this study, and it is essential to tailor interventions according to each patient's overall health, age, and specific cancer attributes. While observation is sometimes the preferred treatment for this age group, two studies drawing data from the National Cancer Database indicated that patients who were solely observed had a lower OS rate than those who received various treatments [21, 22]. Takahashi et al. examined radiotherapy outcomes in patients aged above 80 years with esophageal carcinoma and reported 3-year OS and PFS of 74.1% and 52%, respectively, for patients with stage I disease [23].

The results of the present study emphasize the importance of judicious decision-making related to the inclusion of prophylactic lymph node regions in the radiation field, especially in facilities inclined to administer CRT or IFRT alone for safety purposes. Although minimal lymph node metastases were observed following IFRT in the present study, an extensive prophylactic irradiation field was not considered imperative. Notably, 46% of our cohort had received cancer treatment previously. Nevertheless, favorable outcomes were observed, partly due to the effectiveness of salvage therapies for recurrent tumors and the low incidence of late AEs, especially pulmonary or cardiac complications. In patients with Mt and Lt lesions, IFRT may not significantly reduce the radiation dose delivered to the heart. However, this study's relatively low incidence of cardiac AEs may be attributable to the four-portal irradiation, which reduced the radiation dose per fraction to the heart, and the low proportion of patients who received concurrent chemotherapy. Interestingly, all four out-of-field lymph node recurrences the irradiated field were observed above the irradiation field. These may have been inadequate pretreatment diagnoses of potential lymph node metastases in the superior mediastinum, including thoracic paratracheal lymph node. Local recurrences and the accuracy of pretreatment diagnosis are closely related. Advanced diagnostic tools, such as PET, have proven helpful in detecting lymph nodes and may be necessary for pretreatment PET, especially in T1b patients. It is also important to predict future lymph node recurrence and set the initial irradiation field to allow salvage irradiation after recurrence in advance. In addition, since local (in-field) recurrences in T1b group are apparently noticeable, it may be necessary to increase the intensity of treatment, if possible, by increasing the prescribed dose or by combining this treatment with chemotherapy.

Post-radiotherapy treatments for residual or recurrent esophageal carcinoma vary, with PDT, EMR, and APC being the primary methods. PDT is minimally invasive, and the widespread use of EMR is limited by technical constraints [24, 25]. In contrast, the efficacy of APC is questionable, although its safety profile is commendable [26].

The treatment modalities for older adults represent an important focus of this study, and it is essential to tailor interventions according to each patient’s overall health, age, and specific cancer attributes. In this study, we propose IFRT for esophageal carcinoma in older patients at a dose of 50.4 Gy in 28 fractions with chemotherapy, while IFRT at a dose of ≥ 59.4 Gy for patients who cannot receive chemotherapy or T1b.

The present study had some limitations. The attending physician had discretion over prescription doses and the decision to use concurrent chemotherapy, as these were not standardized. A comprehensive assessment of late toxicity in esophageal cancer was not possible because the study was retrospective and conducted at a single institution, the patient cohort demonstrated significant differences, and the median follow-up duration was 57 months. Patients with relatively short observation durations were included, and the toxicity analysis may have been inadequate. Such findings should be interpreted with caution. Further studies with a longer follow-up duration, greater sample diversity, and inter-institutional collaborations will strengthen the evidence base. Lastly, while standard radiation approaches, such as an extensive irradiation field, may be optimal for younger patients, they may not align with the needs of older individuals due to the potentially severe AEs.