- TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1. - Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. - There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. - There was a trend toward better OS in TRG2 – 3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.. - The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. - If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. - To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.. - The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.. - Neoadjuvant chemo- therapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) are common strategies that have been shown to improve the prognosis of patients with advanced esophageal cancer [1–5]. - Histological evaluation of surgical specimens resected after neoadjuvant therapy can provide valuable informa- tion about the prognosis of patients with esophageal cancer. - Currently, little is known about the pattern and timing of disease recurrence in patients with thoracic esopha- geal squamous cell carcinoma (TESCC) treated with NACRT followed by surgery. - In the present study, therefore, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG in an effort to gain insight into a treatment strategy that improves the prog- nosis of NACRT non-responders.. - Patients with a supraclavicular lymph node (cM1 lymph node) were included [14]. - As a result, in nearly all patients the upper-to-lower mediastinum was included in the irradiated fields.. - In the remaining patients, laparoscopic (including robot- assisted laparoscopic) reconstruction using a pedicled colon was introduced.. - In the present study, however, we used the classification de- fined by the Japanese Classification of Esophageal Can- cer instead of the CAP cancer protocol to more objectively and clearly define the residual cancer (non- responder). - There were no TRG3 patients with locoregio- nal recurrence, and the rate of locoregional recurrence was significantly (P = 0.040) higher in the TRG1 group than in the TRG2 or TRG3 group (Table 2).. - Distant metastasis occurred most fre- quently in the lung (33.3%) followed by an extra-regional lymph node (20.5. - Recurrence in an extra-regional lymph node was observed in all three groups but was detected most frequently in the TRG2 group, where it was detected in 27.3% of patients with recurrence. - There was no significant difference in the median time to first recurrence among the three TRG groups (P = 0.258). - There was no significant differ- ence in median time to first locoregional or distant recurrence in all patients (P = 0.794) or in the TRG1 group (P = 0.811). - (9/22 patients), and 60% (3/5 patients) in the TRG1, TRG2, and TRG3 groups, respectively (P = 0.580).. - Comparison between recurrent patients in the TRG1 group and the combined TRG2/3 group re- vealed a tendency toward better 5-year OS in recurrent patients in the TRG2/3 group than the TRG1 group, but the difference was not statistically significant (P = 0.111,. - Similarly, within the TRG1 group, there was no signifi- cant difference in 5-year OS between patients with locoregional recurrence and those with distant recur- rence (P = 0.895, Fig. - 3 Kaplan-Meier survival curves showing OS in the TRG1 (Red, n = 42), TRG2 (Green, n = 56) and TRG3 (Blue, n = 29) groups (A). - however, the rate of locoregional recurrence was higher in the TRG1 group (36.4%) than the TRG2 or TRG3 group (9.1% or 0. - 60% (3/5 patients) in the TRG1, TRG2, and TRG3 groups, respectively (P = 0.580). - Third, there was a trend toward better OS in the combined TRG2/3 group than the TRG1 group. - That said, patients with recurrence had poorer prognoses, irrespective of TRG or pattern of recurrence.. - 4 Kaplan-Meier survival curves comparing OS between patients with locoregional (orange, n = 10) or distant (purple, n = 14) recurrence: all patients (A), TRG1 patients (B). - In the present study, TRG3 (in other words a pCR) was observed in 23% of ESCC patients. - Differ- ences in the backgrounds of the patients and the chemo- therapy regimens used may explain the difference in the pCR rate between the CROSS trial and the present study. - For instance, only 65% of the patients in the CROSS trial were positive for lymph node metastasis, whereas 91% of the patients were positive for lymph node metastasis prior to treatment in the present study.. - Nevertheless, the 5-year OS rate in this study was similar to or higher than in the CROSS trial. - On the other hand, Smit et al.. - In the present study, we found that the first re- currence was locoregional in 20.4% of patients and was distant in 79.6% of patients. - Hagen et al. - reported no significant difference in the time to locoregional or distant recurrence between complete and incomplete responders [29]. - Oppedijk et al. - In the present study, we found that about 50% of recurrences occurred within the first year, and most recurrences were within 3 years after surgery. - How- ever, because of the small number of recurrence cases, es- pecially locoregional recurrences, in the TRG2 and TRG3 groups, it was difficult to compare the timing of locoregio- nal and distant recurrences among the three TRG groups.. - The first recurrence tended to be earlier in the TRG1 group than the TRG2 group, irrespective of the recurrence pattern, but the difference was not significant.. - Although the 5-year OS rates were better in the TRG2 and TRG3 groups than in the TRG1 group, 39% of TRG2 patients and 17% of TRG3 patients had recur- rences. - Recently, Kelly et al. - 0.001) after surgery in esophageal or gastro-esophageal junction cancer patients with residual pathological dis- ease (ypT +/ypN+) after NACRT [30]. - 3 patients had better prognoses, though the prognoses of patients with distant recurrences were poor. - 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