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.