PMC7493754_01
Timeline of five cycles treatment for the patient and the whole treatment process. Dx indicates diagnosis. PR, Partial Response; PD, Progressive Disease. (A) The patient received the PD-1 inhibitor on the first day and then was treated with SBRT (3 doses of 8 Gy, daily) for one metastatic lesion in the right lung. On the second day after SBRT, GM-CSF 200 mug daily was subcutaneously injected for 2 weeks. This course was repeated every 3 weeks and three courses of triple-combination therapy were administrated in total. Then the patient continued to receive two cycles of sintilimab (200 mg/q3w) after triple-combination therapy. (B) The patient experienced tumor progression after chemoradiotherapy and targeted therapy. After three cycles of triple-combination therapy and two cycles of sintilimab, the patient's progression-free survival period reached 4 months and eventually died of respiratory failure.
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F1
Immunohistochemical staining of the tumor tissue showed that the PD-L1 expression was <1% (Supplementary Figure 1). Three courses of triple-combination therapy were administrated in total and every course was targeted different metastases with SBRT (Figure 1A, Supplementary Figures 3-5). In July 2019, the patient was diagnosed with new brain metastases with a Response Evaluation Criteria in Solid Tumors (RECIST1.1) score of PD (progressive disease) and progression-free survival (PFS) of 4 months (Figure 1B). Eventually, the patient and family members refused ventilator-assisted ventilation and died of respiratory failure in August 2019 (Figure 1B).
Chest CT scans before and after three cycles of triple-combination therapy and two cycles of sintilimab treatment. (A-D) CT revealed that the irradiated right lung lesions shrunk or even disappeared. The arrow in A is the first lesion of the right lung SBRT. The arrow in (B,C) are the second lesions of the right lung SBRT. The arrow in (D) is the third lesion of the right lung SBRT. (E,F) The unirradiated metastatic lesion of the lung was significantly smaller than that before treatment. (G) After five cycles of treatment, the CT scan showed that the unirradiated lesions in right lung had disappeared.
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F2
Imaging assessment was performed after three cycles of triple-combination treatment, which revealed remarkable tumor regression at both the irradiated sites and distant unirradiated sites (Figure 2). However, only the mediastinal lymph nodes enlarged (Supplementary Figures 2B,F). Later, the enlarged lymph nodes shrunk, indicating that the prior change in the lesion was pseudo-progression (Supplementary Figures 2D,H).
Comparison of tumor burden before treatment and after 2 months of triple-combination therapy. After 2 months of treatment, the patient's tumor burden significantly reduced (The tumor volume data was measured by two doctors, the measurement error of each lesion is <2 mm and we finally took the average value). Tumor baseline: Sum of longest diameter of all measurable lesions. RECIST1.1 Target lesions: According to the standard of RECIST1.1, each organ can select at most two lesions as target lesions, so we randomly selected two lung metastatic lesions as target lesions before treatment. Non-target lesions: All measurable metastatic lesions except target lesions. Irradiated lesions: All the SBRT lesions. Considering that the regression of the lesion after radiotherapy will affect the real curative effect, the target lesions is not selected as the SBRT lesions. Unirradiated lesions: All measurable metastatic lesions except SBRT lesions.
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F3
Three courses of triple-combination therapy were administrated in total and every course was targeted different metastases with SBRT (Figure 1A, Supplementary Figures 3-5). Given the significant reduction of tumor burden (Figure 3), the patient continued to receive two cycles of sintilimab (200 mg/q3w) after triple-combination therapy.
CT comparison of the patient's lung inflammation during anti-infective treatment. (A) After three cycles of triple-combination therapy and two cycles of sintilimab monotherapy, chest computed tomography showed inflammatory changes in the lungs and partial lung consolidation. (B,C) The chest CT showed that pulmonary infiltration was absorbed after taking a sufficient amount of steroids and antibiotics. (D) The patient had a "flare" of pneumonitis symptoms when quickly tapered off steroids.
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F4
Three courses of triple-combination therapy were administrated in total and every course was targeted different metastases with SBRT (Figure 1A, Supplementary Figures 3-5). Chest computed tomography showed inflammatory changes in the lungs and partial lung consolidation (Figure 4A) and sputum culture suggested Acinetobacter epidermidis infection, considering radiation pneumonia combined with bacterial infection, immune-related pneumonia cannot be ruled out. The chest CT showed that pulmonary infiltration was absorbed and the patient was discharged (Figures 4B,C). We followed up the patient's chest CT (Figure 4D) and continued to administrate steroids and antibiotics.