Case
A 66-year-old man was diagnosed with advanced ESCC (Mt-Lt, cT3N2M1, stage IVb). After neoadjuvant chemotherapy (1 × 5-fluorouracil+cisplatin and 1 × docetaxel+5-fluorouracil+cisplatin), he underwent esophagostomy with regional lymph node dissection. Tegafur/gimeracil/oteracil (S-1) was started as postoperative adjuvant chemotherapy from 2 months after the esophagostomy. Six months after esophagostomy, left-side cervical and abdominal para-aortal lymph node metastasis was detected on computed tomography (CT) (shown in Fig. 1A). Then, S-1 was discontinued and nivolumab 240 mg per body was administered as second-line treatment 6 times every 2 weeks. Two months later, a follow-up CT scan showed that all metastatic lymph nodes progressed, especially the left cervical lymph node (shown in Fig. 1B). In other words, these tumors were nivolumab resistant. To treat left-side neck pain caused by the progressed metastatic lymph nodes, as a palliative treatment, a total of 40 Gy (10 fractions) of RT was administered using the intensity-modulated, image-guided technique (shown in Fig. 1C).
Nivolumab was resumed the day after completion of RT. A CT scan at 3 months after RT showed that the irradiated lesion in the left neck had regressed to a scar-like appearance. Notably, the abdominal para-aortal lymph nodes outside the irradiation area, which had previously tended to progress, had also shrunk (shown in Fig. 1D). Adverse events were grade 1 oral mucositis, dry skin, pruritus, and fatigue, and no grade 2 or higher adverse events have been observed in combination with RT to date. All the adverse events were associated with nivolumab and not with RT.
The TCR and BCR repertoire analysis was outsourced to Repertoire Genesis Inc. (Tokyo, Japan). The diversity indexes of the TCR and BCR repertoire analysis before and after RT are shown in table 1 and 2. All the diversity indexes in both the TCR and BCR repertoires decreased after RT. The number of unique clones accounting for >0.01% and >0.1% of total TCRs/BCRs before and after RT are shown in Figure 2A, and the top 10 clones of TCRs/BCRs after RT compared with before RT are shown in Figure 2B. There were decreases in the number of unique clones accounting for >0.01% of total TCRs/BCRs before and after RT (TCR: 1795–884, BCR: 1792–1212) and large increases in that of unique clones accounting for >0.1% of total TCRs/BCRs before and after RT (TCR: 60–179, BCR: 130–241). The top 10 clones were mostly similar in the TCR repertoire (8 of the top 10 clones before RT were still in the top 10 clones after RT), but there were some changes (the percentages of the 1st, 2nd, and 4th clones increased more than 0.5%). In the BCR repertoire, all the top 10 clones before RT were replaced after RT. Furthermore, 9 of the 10 clones were newly detected after RT.
Thereafter, the irradiated tumors showed complete response (for 11 months). However, re-progression of the abdominal para-aortal lymph nodes was detected at 7 months after RT, and they were irradiated. Nivolumab was stopped due to nivolumab-related skin rash (out of the irradiated area) at 10 months after the first RT (3 months after the second RT). At 11 months after the first RT, new lymph node metastases (inguinal and axillary) were detected, and the patient is living with the disease.