PMC8443792_01
The variation of the tumor and inflammation in Chest CT. (A) Pre-immunotherapy: the tumor was seen in the right lung; (B) 2 weeks after immunotherapy: patchy shadows appeared around the tumor and air holes occurred in the tumor; (C) 4 weeks after immunotherapy: more air holes developed in the tumor and patchy shadows; (D) 5 weeks after immunotherapy: the tumor and patchy shadows were dissipating; (E, F) 8/12 weeks after immunotherapy: the tumor disappeared, with several linear shadows leaving; (G) 16 weeks after immunotherapy: the tumor reappeared in original site; (H) 18 weeks after immunotherapy: the tumor enlarged.
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A computerized tomography (CT) of chest scan showed the presence of the tumor before ICI treatment (Figure 1A), and two weeks after the treatment, interstitial pneumonia appeared around the tumor (Figure 1B). Following the treatment, the tumor lesion and inflammation around the tumor both diminished gradually until the final disappearance (Figures 1C-F). Despite this initial success, cancer reoccurred in the right lung 4 months after the termination of ICI treatment (Figures 1G, H).
(A) Myositis: the level of serum creatase was used to monitor immune related myositis after immunotherapy; (B) Myocarditis+ Hepatitis: cardiac markers and hepatic transaminase were used to monitor myocarditis and hepatitis, respectively, after immunotherapy; (C) Pituitary-Adrenal Axis: the level of COR and ACTH were used to monitor the function of the pituitary-adrenal axis: COR and ACTH both declined remarkably after ICI therapy; ACTH was maintained at a low level while COR was still lower than the normal value by glucocorticoid replacement therapy; (D) Pituitary-Gonad Axis: the level of FSH, LH, and TESTO were used to monitor the function of the pituitary-gonad axis: all of them fluctuated in the range of normal values; TSH and FT4 were both normal in the pituitary-thyroid axis; (E) Autoimmune Reponse: IL-6 and TNF-alpha was used to monitor the autoimmune response induce by ICI: IL-6 fluctuated beyond the upper limit of normal (ULN) while TNF-alpha fell to normal gradually after glucocorticoid replacement therapy; (F) Tumor Marker: tumor markers was used to monitor efficacy of ICI.
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An increase in serum interleukin-6 (IL-6) and tumor necrosis factor (TNF) was detected (Figure 2E). Serum levels of creatine kinase (CK), lactic dehydrogenase (LDH), and alpha-hydroxybutyric dehydrogenase (alpha-HBDH) had increased (Figure 2A). The level of cardiac troponin T (TNT) was remarkably high (Figure 2B). Both serum glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) also increased (Figure 2B). The level of cortisol (COR) and adrenocorticotrophic hormone (ACTH) was lower than normal values from April 17, which fluctuated following glucocorticoid therapy (Figure 2C). The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (TESTO) were normal, yet transitorily lower than the base value on April 17, while thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were normal. (Figure 2D). Meanwhile, the serum tumor markers (CA125, CYFRA211, and CEA) showed a downward trend (Figure 2F).
(A) Muscle MRI of 5 weeks after immunotherapy: diffuse strip-shaped high-signal shadows were seen in the back and lower limbs, as indicated by the red arrows; (B) Muscle MRI of 10 weeks after immunotherapy: high-signal shadows receded after 40 days of glucocorticoid treatment, especially in the right lower limbs, as indicated by the red arrows.
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Magnetic resonance imaging (MRI) found a diffuse exudation in the muscles of the backside and lower limbs (Figure 3A). And the diffuse exudation reduced in the muscles of the right lower limbs (Figure 3B).
The process of diagnosis and treatment of irAEs after ICI therapy. P, prednisone; MP, methylprednisolone; GS, glucose solution; NS, normal saline; TGP, total glucosides of paeonia; Co-Q, coenzyme Q; FDP, fructose1, 6-diphosphate. Note: The grade of irAEs refer to the management of immunotherapy-related toxicities from the NCCN clinical practice guidelines and the consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.
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The therapeutic process of irAEs is shown in Figure 4.