PMC7884808_01
The time line, biomarker and medical imaging information of the patient. (A) Time axis of antitumor treatment and intervention in terms of side effects. (T = paclitaxel; S = S-1; G = gemcitabine; Bev = bevacizumab; Nivo = nivolumab), Karnofsky Performance Status (KPS) refer to the Karnofsky performance status during that period. (B) Carcinoembryonic antigen (CEA) levels during treatment; (C) CA125 levels during treatment. Chest CT images showing the tumors on lungs: (D) The initial images at the time of diagnosis showed multiple pulmonary metastases and bronchial obstruction; (E) The images of the same lesion before the immunotherapy; (F) The pulmonary metastases were enlarged transiently on the first follow-up examination; (G) The lesion was decreased after the subsequent two cycles of treatment; (H) Further tumor shrinking on the latest follow-up images, the lesion in right inferior lobar almost disappeared. Positron emission tomography (PET)/computed tomography (CT) of the patient: The left panel of each picture shows the initial image of the lung metastases, and the right panel shows the images of the same lesions 10 months after the termination of immune checkpoint inhibitor (ICI) treatment: (I) Metastatic tumor in the right lung; (J) Metastatic tumor in the left lung; (K) Paraaortic node metastases and lesions disappeared after treatment.
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Further positron emission tomography (PET) showed tumors in the lungs and paraaortic lymph nodes ( Figures 1D, I-K ). After another six cycles of treatment, the patient had a better performance status and stable disease of his lungs ( Figure 1E ) and urinary tract. However, in August 2018 (at the evaluation after two cycles), the CT scan revealed that the lesions in the lungs were significantly enlarged (largest lesion from baseline 30 mm to 43 mm,  Figure 1F ) with elevated tumor biomarkers cancer antigen (CA) 125 and carcinoembryonic antigen (CEA) ( Figures 1B, C ), while the patient had no obvious symptoms or signs. On the next follow-up CT (6 weeks after sustained treatment), the sizes of the tumors in the lungs had markedly decreased ( Figure 1G ), and his residual lesion in paraaortic node disappeared. Surprisingly, a PET scan in June 2019 revealed that the tumors in the lungs and paraaortic lymph nodes were reduced with no abnormal metabolic activity ( Figures 1I-K ). The last CT scans were performed in September 2020, and there was still no sign of tumor progression ( Figure 1H ).
Chest computed tomography (CT) images showing the ICI-related pneumonitis (CIP) (A) ground-glass opacity in both lungs. (B) Inflammation absorbed after 2 weeks of glucocorticoid treatment. (C) CIP recurrence after resuming nivolumab treatment. Ground-glass opacity (GGO) reoccurred, and more lobes of the left lung were involved. (D) During the period of recurrent CIP, both lungs showed diffuse GGO, consolidation and the air bronchus-charging sign. (E) Image after 7 days of corticosteroid pulse therapy. The extent of CIP was reduced. (F) Image after 4 months of CIP treatment. The signs of pneumonitis subsided.
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Chest radiography revealed diffuse ground-glass opacity (GGO) in both lungs without progression of metastatic tumor lesions ( Figure 2A ). The symptoms and radiography showed obvious improvement ( Figure 2B ). Radiography showed more GGO in the lungs ( Figure 2C ), and the percutaneous oxygen saturation (SpO2) was 93%. Two weeks later, the patient's symptoms were aggravated again, and pneumonitis progressed in multiple lobes ( Figure 2D ). His symptoms improved gradually after 8 weeks of steroid treatment, and he ultimately recovered ( Figures 2E, F ).