PMC9768626_01
Diagnosis, treatment regimens, immune-related adverse events, and biomarker levels in the lung cancer patients. Neutrophile to Lymphocyte Ratio (NLR), C-Reactive Protein (CRP), and Thyroid Stimulating Hormone (TSH) levels are shown along with the treatment and immune-related adverse events (irAEs). (A) Patient #1. The patient had a 5-year history (-1801 days) of inoperable stage IIIA (T1aN2M0) right upper lobe (RUL) lung adenocarcinoma. He was initially treated with chemoradiation, followed by disease progression. He then received 8 doses of bi-weekly 240 mg Nivolumab (days 0 to 106) and was enrolled in the biomarker study. Checkpoint inhibitor-induced thyroid dysfunction (CITD, thyroiditis) was observed as an immune-related adverse event (irAE) after the 2nd dose of Nivolumab (C2). Later, the patient received another round of Nivolumab treatment (days 439 to 621, not enrolled in our biomarker trial) in which pneumonitis as another irAE occurred (day 621). (B) Patient #2. The patient was diagnosed with RUL squamous cell carcinoma (-429 days) and received chemoradiation. Subsequent PET scan demonstrated a complete metabolic response (CMR). Unfortunately, 7 months later he had recurrence of RUL mass. The patient received 7 cycles of bi-weekly 240 mg Nivolumab treatment (days 0 to 84) when enrolled in our biomarker study. CIDT (thyroiditis) was detected after the 4th dose of Nivolumab (C4). Later, the patient received another round of Nivolumab treatment (days 140 to 259, not enrolled in our biomarker trial) in which another irAE, intestinal perforation, occurred (day 267).
fonc-12-1023545-g001.jpg
PMC9768626_02_fonc-12-1023545-g001.jpg
f1
After 4 cycles of nivolumab, routine TSH measurements revealed an increase above the upper limit of normal to 28.82 mIU/L on cycle 6, with a slight prior decrease in TSH on cycle 2 and 3 ( Figure 1B  and  Supplementary Figure 1B ). Upon completing the 9th cycle of nivolumab, the patient developed an intestinal perforation of undifferentiated etiology and succumbed to the complications of his disease ( Figure 1B  and  Supplementary Figure 2 ).
PMC9768626_02
Diagnosis, treatment regimens, immune-related adverse events, and biomarker levels in the lung cancer patients. Neutrophile to Lymphocyte Ratio (NLR), C-Reactive Protein (CRP), and Thyroid Stimulating Hormone (TSH) levels are shown along with the treatment and immune-related adverse events (irAEs). (A) Patient #1. The patient had a 5-year history (-1801 days) of inoperable stage IIIA (T1aN2M0) right upper lobe (RUL) lung adenocarcinoma. He was initially treated with chemoradiation, followed by disease progression. He then received 8 doses of bi-weekly 240 mg Nivolumab (days 0 to 106) and was enrolled in the biomarker study. Checkpoint inhibitor-induced thyroid dysfunction (CITD, thyroiditis) was observed as an immune-related adverse event (irAE) after the 2nd dose of Nivolumab (C2). Later, the patient received another round of Nivolumab treatment (days 439 to 621, not enrolled in our biomarker trial) in which pneumonitis as another irAE occurred (day 621). (B) Patient #2. The patient was diagnosed with RUL squamous cell carcinoma (-429 days) and received chemoradiation. Subsequent PET scan demonstrated a complete metabolic response (CMR). Unfortunately, 7 months later he had recurrence of RUL mass. The patient received 7 cycles of bi-weekly 240 mg Nivolumab treatment (days 0 to 84) when enrolled in our biomarker study. CIDT (thyroiditis) was detected after the 4th dose of Nivolumab (C4). Later, the patient received another round of Nivolumab treatment (days 140 to 259, not enrolled in our biomarker trial) in which another irAE, intestinal perforation, occurred (day 267).
fonc-12-1023545-g001.jpg
PMC9768626_02_fonc-12-1023545-g001.jpg
f1
After 4 cycles of nivolumab, routine TSH measurements revealed an increase above the upper limit of normal to 28.82 mIU/L on cycle 6, with a slight prior decrease in TSH on cycle 2 and 3 ( Figure 1B  and  Supplementary Figure 1B ). Upon completing the 9th cycle of nivolumab, the patient developed an intestinal perforation of undifferentiated etiology and succumbed to the complications of his disease ( Figure 1B  and  Supplementary Figure 2 ).
Dynamic changes of peripheral blood CD4+ T cells, CD8+ T cells, and inflammatory cytokines in the lung cancer patients treated with Nivolumab. Blood samples were collected at the baseline and after each cycle of Nivolumab treatment during the biomarker trial. Baseline: values from the blood samples collected before the Nivolumab treatment initiation; Cycle 1: values after the 1st dose of Nivolumab, from the blood samples collected right before the second dose administration; Cycle 2: values after the 2nd dose of Nivolumab, from the blood samples collected right before the third dose administration, and so on. (A, B) Percent change of peripheral CD4+ T cells and CD8+ T cells from baseline after each dose of Nivolumab in patient #1 and #2, respectively. (C, D) Plasma IL-6, IL-17, TNF-alpha, INF-gamma, and IL-1beta levels in patient #1 and #2, respectively. Onset of checkpoint inhibitor-induced thyroid dysfunction (CITD) is indicated by arrows on the graphs.
fonc-12-1023545-g002.jpg
PMC9768626_02_fonc-12-1023545-g002.jpg
f2
Upon completing the 9th cycle of nivolumab, the patient developed an intestinal perforation of undifferentiated etiology and succumbed to the complications of his disease ( Figure 1B  and  Supplementary Figure 2 ).