PMC7443410_01
The CT scan of the patients before surgery. (A) The 4 cm tumor on the right upper lobe (Red arrow); (B) Metastatic right No.4 lymph node (Red arrow).
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Immunohistochemical staining. (A) Hematoxylin-eosin staining of the tumor tissue (40X and 400X); (B) Immunohistochemical staining for Synaptophysin (Positive, 400X); (C) Immunohistochemical staining for Chromogranin A (Positive, 400X); (D) Immunohistochemical staining for Ki-67 (80% Positive, 400X).
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A and Ki-67 (80%), focal positive staining for CK7, CD56 and CD117, but negative staining for CK5/6, P40, P63, CD45 (LCA) and PSA-AB, consistent with a LCNELC origin (Figure 2). Adjuvant chemotherapy was rejected by the patient.
Abdominal CT scan of the metastatic tumor in left adrenal gland before and during the treatment course. (A) Metastatic tumor in left adrenal gland before the treatment of nivolumab (Red arrow). (B) Metastatic tumor in left adrenal gland after 4 cycles treatment of nivolumab (Red arrow); (C) Metastatic tumor in left adrenal gland after 8 cycles treatment of nivolumab (Red arrow); (D) Metastatic tumor in left adrenal gland after 12 cycles treatment of nivolumab (Red arrow); (E) Metastatic tumor in left adrenal gland after 15 cycles treatment of nivolumab (Red arrow); (F) Metastatic tumor in left adrenal gland after 3 months since the drug withdrawal (Red arrow); (G) Metastatic tumor in left adrenal gland after 7 months since the drug withdrawal (Red arrow); (H) Metastatic tumor in left adrenal gland after 12 months since the drug withdrawal (Red arrow).
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The scans revealed a 2-cm-sized metastatic tumor in the left adrenal gland, which indicated progressive disease (Figure 3A). During 15 cycles of treatment, the patient achieved a complete response (CR), with significant regression of the metastatic tumor in the left adrenal gland (Figure 3B-E). By 4, 8 and 12 months after drug withdrawal, no progression occurred (Figure 3F-H) and the level of NSE remained in the normal range (Figure 6A).
Immunohistochemical staining of primary tumor in lung for PD-L1. (A) Hematoxylin-eosin staining of the tumor tissue (200X). (B) Immunohistochemical staining for PD-L1 (Negative, 200X).
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Chest CT scan of the interstitial pneumonia related to nivolumab treatment before and during the treatment course by acetylcysteine and corticosteroids. (A) Interlobular septal thickening and subpleural ground-glass opacities before the 16th cycle of nivolumab treatment (Red arrow). (B) Interlobular septal thickening and subpleural ground-glass opacities got worse in 3 months after nivolumab withdrawal (Red arrow). (C) Interlobular septal thickening and subpleural ground-glass opacities got better in 4 months since acetylcysteine and corticosteroids treatment (Red arrow). D. Interlobular septal thickening and subpleural ground-glass opacities disappeared in 4 months since acetylcysteine and corticosteroids withdrawal (Red arrow).
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Before the 16th cycle of treatment, the patient suffered from cough with mild dyspnea and a chest CT showed interlobular septal thickening and subpleural ground-glass opacities (Figure 5A). Nivolumab therapy was discontinued for 3 months but the symptoms and conditions revealed by the CT images became worse (Figure 5B). By treating the patient with acetylcysteine and corticosteroids for 3 months, the symptoms disappeared and the CT imaging results recovered (Figure 5C and D).
The efficiency of the treatment evaluated by blood test. (A) NSE detected in serum before and during the treatment course. (B) ctDNA tested via NGS before and after 2, 4 cycles after nivolumab treatment.
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By 4, 8 and 12 months after drug withdrawal, no progression occurred (Figure 3F-H) and the level of NSE remained in the normal range (Figure 6A). DNA (ctDNA) from three sequential plasma samples collected before, and two and four cycles after nivolumab treatment showed a continued decrease during the treatment course, which indicated a durable response to nivolumab (Figure 6B). During 20 months of post-treatment follow-up (until May 2020), no recurrence or metastasis was observed in the patient.